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</button> <ul id="toc-Mechanism_of_action-sublist" class="vector-toc-list"> <li id="toc-VEGF_pathway_inhibition" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#VEGF_pathway_inhibition"> <div class="vector-toc-text"> <span class="vector-toc-numb">1.1</span> <span>VEGF pathway inhibition</span> </div> </a> <ul id="toc-VEGF_pathway_inhibition-sublist" class="vector-toc-list"> </ul> </li> </ul> </li> <li id="toc-Endogenous_regulation" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#Endogenous_regulation"> <div class="vector-toc-text"> <span class="vector-toc-numb">2</span> <span>Endogenous regulation</span> </div> </a> <ul id="toc-Endogenous_regulation-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Exogenous_regulation" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#Exogenous_regulation"> <div class="vector-toc-text"> <span class="vector-toc-numb">3</span> <span>Exogenous regulation</span> </div> </a> <button aria-controls="toc-Exogenous_regulation-sublist" class="cdx-button cdx-button--weight-quiet cdx-button--icon-only vector-toc-toggle"> <span class="vector-icon mw-ui-icon-wikimedia-expand"></span> <span>Toggle Exogenous regulation subsection</span> </button> <ul id="toc-Exogenous_regulation-sublist" class="vector-toc-list"> <li id="toc-Diet" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Diet"> <div class="vector-toc-text"> <span class="vector-toc-numb">3.1</span> <span>Diet</span> </div> </a> <ul id="toc-Diet-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Drugs" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Drugs"> <div class="vector-toc-text"> <span class="vector-toc-numb">3.2</span> <span>Drugs</span> </div> </a> <ul id="toc-Drugs-sublist" class="vector-toc-list"> <li id="toc-Overview" class="vector-toc-list-item vector-toc-level-3"> <a class="vector-toc-link" href="#Overview"> <div class="vector-toc-text"> <span class="vector-toc-numb">3.2.1</span> <span>Overview</span> </div> </a> <ul id="toc-Overview-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Bevacizumab" class="vector-toc-list-item vector-toc-level-3"> <a class="vector-toc-link" href="#Bevacizumab"> <div class="vector-toc-text"> <span class="vector-toc-numb">3.2.2</span> <span>Bevacizumab</span> </div> </a> <ul id="toc-Bevacizumab-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Thalidomide" class="vector-toc-list-item vector-toc-level-3"> <a class="vector-toc-link" href="#Thalidomide"> <div class="vector-toc-text"> <span class="vector-toc-numb">3.2.3</span> <span>Thalidomide</span> </div> </a> <ul id="toc-Thalidomide-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Cannabinoids" class="vector-toc-list-item vector-toc-level-3"> <a class="vector-toc-link" href="#Cannabinoids"> <div 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class="vector-toc-text"> <span class="vector-toc-numb">3.3.2</span> <span>Increased blood pressure</span> </div> </a> <ul id="toc-Increased_blood_pressure-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Less_common_side_effects" class="vector-toc-list-item vector-toc-level-3"> <a class="vector-toc-link" href="#Less_common_side_effects"> <div class="vector-toc-text"> <span class="vector-toc-numb">3.3.3</span> <span>Less common side effects</span> </div> </a> <ul id="toc-Less_common_side_effects-sublist" class="vector-toc-list"> </ul> </li> </ul> </li> </ul> </li> <li id="toc-See_also" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#See_also"> <div class="vector-toc-text"> <span class="vector-toc-numb">4</span> <span>See also</span> </div> </a> <ul id="toc-See_also-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-References" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a 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class="vector-unpinned-container"> </div> </div> </div> </nav> <h1 id="firstHeading" class="firstHeading mw-first-heading"><span class="mw-page-title-main">Angiogenesis inhibitor</span></h1> <div id="p-lang-btn" class="vector-dropdown mw-portlet mw-portlet-lang" > <input type="checkbox" id="p-lang-btn-checkbox" role="button" aria-haspopup="true" data-event-name="ui.dropdown-p-lang-btn" class="vector-dropdown-checkbox mw-interlanguage-selector" aria-label="Go to an article in another language. Available in 13 languages" > <label id="p-lang-btn-label" for="p-lang-btn-checkbox" class="vector-dropdown-label cdx-button cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--weight-quiet cdx-button--action-progressive mw-portlet-lang-heading-13" aria-hidden="true" ><span class="vector-icon mw-ui-icon-language-progressive mw-ui-icon-wikimedia-language-progressive"></span> <span class="vector-dropdown-label-text">13 languages</span> </label> <div class="vector-dropdown-content"> <div class="vector-menu-content"> <ul class="vector-menu-content-list"> <li class="interlanguage-link interwiki-ar mw-list-item"><a href="https://ar.wikipedia.org/wiki/%D9%85%D8%AB%D8%A8%D8%B7_%D8%AA%D9%83%D9%88%D9%86_%D8%A7%D9%84%D8%A3%D9%88%D8%B9%D9%8A%D8%A9" title="مثبط تكون الأوعية – Arabic" lang="ar" hreflang="ar" data-title="مثبط تكون الأوعية" data-language-autonym="العربية" data-language-local-name="Arabic" class="interlanguage-link-target"><span>العربية</span></a></li><li class="interlanguage-link interwiki-ca mw-list-item"><a href="https://ca.wikipedia.org/wiki/Antiangiog%C3%A8nic" title="Antiangiogènic – Catalan" lang="ca" hreflang="ca" data-title="Antiangiogènic" data-language-autonym="Català" data-language-local-name="Catalan" class="interlanguage-link-target"><span>Català</span></a></li><li class="interlanguage-link interwiki-de mw-list-item"><a href="https://de.wikipedia.org/wiki/Antiangiogenese" title="Antiangiogenese – German" lang="de" hreflang="de" data-title="Antiangiogenese" data-language-autonym="Deutsch" data-language-local-name="German" class="interlanguage-link-target"><span>Deutsch</span></a></li><li class="interlanguage-link interwiki-es mw-list-item"><a href="https://es.wikipedia.org/wiki/Antiangiog%C3%A9nico" title="Antiangiogénico – Spanish" lang="es" hreflang="es" data-title="Antiangiogénico" data-language-autonym="Español" data-language-local-name="Spanish" class="interlanguage-link-target"><span>Español</span></a></li><li class="interlanguage-link interwiki-fa mw-list-item"><a href="https://fa.wikipedia.org/wiki/%D8%A8%D8%A7%D8%B2%D8%AF%D8%A7%D8%B1%D9%86%D8%AF%D9%87_%D8%B1%DA%AF%E2%80%8C%D8%B2%D8%A7%DB%8C%DB%8C" title="بازدارنده رگ‌زایی – Persian" lang="fa" hreflang="fa" data-title="بازدارنده رگ‌زایی" data-language-autonym="فارسی" data-language-local-name="Persian" class="interlanguage-link-target"><span>فارسی</span></a></li><li class="interlanguage-link interwiki-ms mw-list-item"><a href="https://ms.wikipedia.org/wiki/Perencat_angiogenesis" title="Perencat angiogenesis – Malay" lang="ms" hreflang="ms" data-title="Perencat angiogenesis" data-language-autonym="Bahasa Melayu" data-language-local-name="Malay" class="interlanguage-link-target"><span>Bahasa Melayu</span></a></li><li class="interlanguage-link interwiki-nl mw-list-item"><a href="https://nl.wikipedia.org/wiki/Angiogeneseremmer" title="Angiogeneseremmer – Dutch" lang="nl" hreflang="nl" data-title="Angiogeneseremmer" data-language-autonym="Nederlands" data-language-local-name="Dutch" class="interlanguage-link-target"><span>Nederlands</span></a></li><li class="interlanguage-link interwiki-pt mw-list-item"><a href="https://pt.wikipedia.org/wiki/Inibidor_de_angiog%C3%AAnese" title="Inibidor de angiogênese – Portuguese" lang="pt" hreflang="pt" data-title="Inibidor de angiogênese" data-language-autonym="Português" data-language-local-name="Portuguese" class="interlanguage-link-target"><span>Português</span></a></li><li class="interlanguage-link interwiki-ru mw-list-item"><a href="https://ru.wikipedia.org/wiki/%D0%90%D0%BD%D0%B3%D0%B8%D0%BE%D0%B3%D0%B5%D0%BD%D0%BD%D1%8B%D0%B9_%D0%B8%D0%BD%D0%B3%D0%B8%D0%B1%D0%B8%D1%82%D0%BE%D1%80" title="Ангиогенный ингибитор – Russian" lang="ru" hreflang="ru" data-title="Ангиогенный ингибитор" data-language-autonym="Русский" data-language-local-name="Russian" class="interlanguage-link-target"><span>Русский</span></a></li><li class="interlanguage-link interwiki-sr mw-list-item"><a href="https://sr.wikipedia.org/wiki/Inhibitori_angiogeneze" title="Inhibitori angiogeneze – Serbian" lang="sr" hreflang="sr" data-title="Inhibitori angiogeneze" data-language-autonym="Српски / srpski" data-language-local-name="Serbian" class="interlanguage-link-target"><span>Српски / srpski</span></a></li><li class="interlanguage-link interwiki-sh mw-list-item"><a href="https://sh.wikipedia.org/wiki/Inhibitori_angiogeneze" title="Inhibitori angiogeneze – Serbo-Croatian" lang="sh" hreflang="sh" data-title="Inhibitori angiogeneze" data-language-autonym="Srpskohrvatski / српскохрватски" data-language-local-name="Serbo-Croatian" class="interlanguage-link-target"><span>Srpskohrvatski / српскохрватски</span></a></li><li class="interlanguage-link interwiki-sv mw-list-item"><a href="https://sv.wikipedia.org/wiki/Angiogenesh%C3%A4mmare" title="Angiogeneshämmare – Swedish" lang="sv" hreflang="sv" data-title="Angiogeneshämmare" data-language-autonym="Svenska" 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data-pinned-container-id="vector-appearance-pinned-container" data-unpinned-container-id="vector-appearance-unpinned-container" > <div class="vector-pinnable-header-label">Appearance</div> <button class="vector-pinnable-header-toggle-button vector-pinnable-header-pin-button" data-event-name="pinnable-header.vector-appearance.pin">move to sidebar</button> <button class="vector-pinnable-header-toggle-button vector-pinnable-header-unpin-button" data-event-name="pinnable-header.vector-appearance.unpin">hide</button> </div> </div> </div> </nav> </div> </div> <div id="bodyContent" class="vector-body" aria-labelledby="firstHeading" data-mw-ve-target-container> <div class="vector-body-before-content"> <div class="mw-indicators"> </div> <div id="siteSub" class="noprint">From Wikipedia, the free encyclopedia</div> </div> <div id="contentSub"><div id="mw-content-subtitle"><span class="mw-redirectedfrom">(Redirected from <a href="/w/index.php?title=Antiangiogenic&redirect=no" class="mw-redirect" title="Antiangiogenic">Antiangiogenic</a>)</span></div></div> <div id="mw-content-text" class="mw-body-content"><div class="mw-content-ltr mw-parser-output" lang="en" dir="ltr"><div class="shortdescription nomobile noexcerpt noprint searchaux" style="display:none">Substance that inhibits the growth of new blood vessels</div> <p> An <b>angiogenesis inhibitor</b> is a substance that inhibits the growth of new blood vessels (<a href="/wiki/Angiogenesis" title="Angiogenesis">angiogenesis</a>). Some angiogenesis inhibitors are <a href="/wiki/Endogenous" class="mw-redirect" title="Endogenous">endogenous</a> and a normal part of the body's control and others are obtained <a href="/wiki/Exogenously" class="mw-redirect" title="Exogenously">exogenously</a> through <a href="/wiki/Drugs" class="mw-redirect" title="Drugs">pharmaceutical drugs</a> or <a href="/wiki/Diet_(nutrition)" title="Diet (nutrition)">diet</a>. </p><p>While angiogenesis is a critical part of <a href="/wiki/Wound_healing" title="Wound healing">wound healing</a> and other favorable processes, certain types of angiogenesis are associated with the growth of <a href="/wiki/Malignant" class="mw-redirect" title="Malignant">malignant</a> <a href="/wiki/Tumors" class="mw-redirect" title="Tumors">tumors</a>. Thus angiogenesis inhibitors have been closely studied for possible <a href="/wiki/Cancer" title="Cancer">cancer</a> treatment. Angiogenesis inhibitors were once thought to have potential as a "<a href="/wiki/Silver_bullet" title="Silver bullet">silver bullet</a>" treatment applicable to many types of cancer, but the limitations of anti-angiogenic therapy have been shown in practice.<sup id="cite_ref-1" class="reference"><a href="#cite_note-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup> Currently, angiogenesis inhibitors are recognized for their improvement of cancer immunotherapy<sup id="cite_ref-2" class="reference"><a href="#cite_note-2"><span class="cite-bracket">[</span>2<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-3" class="reference"><a href="#cite_note-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup> by overcoming <a href="/wiki/Endothelial_cell_anergy" title="Endothelial cell anergy">endothelial cell anergy</a>. Angiogenesis inhibitors are also used to effectively treat <a href="/wiki/Macular_degeneration" title="Macular degeneration">macular degeneration</a> in the eye, and other diseases that involve a proliferation of blood vessels.<sup id="cite_ref-4" class="reference"><a href="#cite_note-4"><span class="cite-bracket">[</span>4<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-5" class="reference"><a href="#cite_note-5"><span class="cite-bracket">[</span>5<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-6" class="reference"><a href="#cite_note-6"><span class="cite-bracket">[</span>6<span class="cite-bracket">]</span></a></sup> </p> <meta property="mw:PageProp/toc" /> <div class="mw-heading mw-heading2"><h2 id="Mechanism_of_action">Mechanism of action</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Angiogenesis_inhibitor&action=edit&section=1" title="Edit section: Mechanism of action"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>When a tumor stimulates the growth of new vessels, it is said to have undergone an 'angiogenic switch'. The principal stimulus for this angiogenic switch appears to be oxygen deprivation, although other stimuli such as inflammation, oncogenic mutations and mechanical stress may also play a role. The angiogenic switch leads to tumor expression of pro-angiogenic factors and increased tumor vascularization.<sup id="cite_ref-Folkman_J_7-0" class="reference"><a href="#cite_note-Folkman_J-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup> Specifically, <a href="/wiki/Tumor" class="mw-redirect" title="Tumor">tumor</a> cells release various pro-angiogenic <a href="/wiki/Paracrine" class="mw-redirect" title="Paracrine">paracrine</a> factors (including <a href="/wiki/Angiogenin" title="Angiogenin">angiogenin</a>, vascular endothelial growth factor (<a href="/wiki/VEGF" class="mw-redirect" title="VEGF">VEGF</a>), fibroblast growth factor (<a href="/wiki/Fibroblast_growth_factor" title="Fibroblast growth factor">FGF</a>), and transforming growth factor-β (<a href="/wiki/TGF-%CE%B2" class="mw-redirect" title="TGF-β">TGF-β</a>). These stimulate <a href="/wiki/Endothelial_cell" class="mw-redirect" title="Endothelial cell">endothelial cell</a> proliferation, migration and invasion resulting in new vascular structures sprouting from nearby blood vessels.<sup id="cite_ref-8" class="reference"><a href="#cite_note-8"><span class="cite-bracket">[</span>8<span class="cite-bracket">]</span></a></sup> <a href="/wiki/Cell_adhesion_molecule" title="Cell adhesion molecule">Cell adhesion molecules</a>, such as <a href="/wiki/Integrins" class="mw-redirect" title="Integrins">integrins</a>, are critical to the attachment and migration of endothelial cells to the <a href="/wiki/Extracellular_matrix" title="Extracellular matrix">extracellular matrix</a>.<sup id="cite_ref-Folkman_J_7-1" class="reference"><a href="#cite_note-Folkman_J-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="VEGF_pathway_inhibition">VEGF pathway inhibition</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Angiogenesis_inhibitor&action=edit&section=2" title="Edit section: VEGF pathway inhibition"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Inhibiting angiogenesis requires treatment with anti-angiogenic factors, or drugs which reduce the production of pro-angiogenic factors, prevent them binding to their receptors or block their actions. Inhibition of the VEGF pathway has become the focus of angiogenesis research, as approximately 60% of malignant tumors express high concentrations of VEGF. Strategies to inhibit the VEGF pathway include <a href="/wiki/Antibodies" class="mw-redirect" title="Antibodies">antibodies</a> directed against VEGF or VEGFR, soluble VEGFR/VEGFR hybrids, and <a href="/wiki/Tyrosine_kinase_inhibitors" class="mw-redirect" title="Tyrosine kinase inhibitors">tyrosine kinase inhibitors</a>.<sup id="cite_ref-Folkman_J_7-2" class="reference"><a href="#cite_note-Folkman_J-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Cao_9-0" class="reference"><a href="#cite_note-Cao-9"><span class="cite-bracket">[</span>9<span class="cite-bracket">]</span></a></sup> The most widely used VEGF pathway inhibitor on the market today is <a href="/wiki/Bevacizumab" title="Bevacizumab">Bevacizumab</a>.<sup id="cite_ref-10" class="reference"><a href="#cite_note-10"><span class="cite-bracket">[</span>10<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-11" class="reference"><a href="#cite_note-11"><span class="cite-bracket">[</span>11<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-12" class="reference"><a href="#cite_note-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup> Bevacizumab binds to VEGF and inhibits it from binding to VEGF receptors.<sup id="cite_ref-Rini-2007_13-0" class="reference"><a href="#cite_note-Rini-2007-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Endogenous_regulation">Endogenous regulation</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Angiogenesis_inhibitor&action=edit&section=3" title="Edit section: Endogenous regulation"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Angiogenesis is regulated by the activity of endogenous stimulators and inhibitors. Endogenous inhibitors, found in the body naturally, are involved in the day-to-day process of regulating blood vessel formation. Endogenous inhibitors are often derived from the extracellular matrix or basement membrane proteins and function by interfering with <a href="/wiki/Endothelial_cell" class="mw-redirect" title="Endothelial cell">endothelial cell</a> formation and migration, endothelial tube <a href="/wiki/Morphogenesis" title="Morphogenesis">morphogenesis</a>, and <a href="/wiki/Downregulation_and_upregulation" title="Downregulation and upregulation">down-regulation</a> of genes expressed in endothelial cells. </p><p>During tumor growth, the action of angiogenesis stimulators surpasses the control of angiogenesis inhibitors, allowing for unregulated or less regulated blood vessel growth and formation.<sup id="cite_ref-Nyberg_P,_Xie_L,_Kalluri_R_3967–79_14-0" class="reference"><a href="#cite_note-Nyberg_P,_Xie_L,_Kalluri_R_3967–79-14"><span class="cite-bracket">[</span>14<span class="cite-bracket">]</span></a></sup> Endogenous inhibitors are attractive targets for <a href="/wiki/Cancer_therapy" class="mw-redirect" title="Cancer therapy">cancer therapy</a> because they are less toxic and less likely to lead to drug resistance than some exogenous inhibitors.<sup id="cite_ref-Folkman_J_7-3" class="reference"><a href="#cite_note-Folkman_J-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Cao_9-1" class="reference"><a href="#cite_note-Cao-9"><span class="cite-bracket">[</span>9<span class="cite-bracket">]</span></a></sup> However, the therapeutic use of endogenous inhibitors has disadvantages. In animal studies, high doses of inhibitors were required to prevent tumor growth and the use of endogenous inhibitors would likely be long-term.<sup id="cite_ref-Nyberg_P,_Xie_L,_Kalluri_R_3967–79_14-1" class="reference"><a href="#cite_note-Nyberg_P,_Xie_L,_Kalluri_R_3967–79-14"><span class="cite-bracket">[</span>14<span class="cite-bracket">]</span></a></sup> </p> <table class="wikitable"> <tbody><tr> <th>Inhibitors</th> <th>Mechanism </th></tr> <tr> <td>soluble <a href="/wiki/VEGFR-1" class="mw-redirect" title="VEGFR-1">VEGFR-1</a> and <a href="/wiki/NRP-1" class="mw-redirect" title="NRP-1">NRP-1</a></td> <td><a href="/wiki/Decoy_receptor" class="mw-redirect" title="Decoy receptor">decoy receptors</a><sup id="cite_ref-15" class="reference"><a href="#cite_note-15"><span class="cite-bracket">[</span>15<span class="cite-bracket">]</span></a></sup> for <a href="/wiki/Vascular_endothelial_growth_factor" title="Vascular endothelial growth factor">VEGF</a>-B and <a href="/wiki/PIGF" title="PIGF">PIGF</a> </td></tr> <tr> <td><a href="/wiki/Angiopoietin_2" class="mw-redirect" title="Angiopoietin 2">Angiopoietin 2</a></td> <td>antagonist of <a href="/wiki/Angiopoietin_1" title="Angiopoietin 1">angiopoietin 1</a> </td></tr> <tr> <td><a href="/wiki/Thrombospondin_1" title="Thrombospondin 1">TSP-1</a> and <a href="/wiki/Thrombospondin" title="Thrombospondin">TSP-2</a></td> <td>inhibit <a href="/wiki/Cell_migration" title="Cell migration">cell migration</a>, <a href="/wiki/Cell_proliferation" title="Cell proliferation">cell proliferation</a>, <a href="/wiki/Cell_adhesion" title="Cell adhesion">cell adhesion</a> and survival of <a href="/wiki/Endothelium" title="Endothelium">endothelial cells</a> </td></tr> <tr> <td><a href="/wiki/Angiostatin" title="Angiostatin">angiostatin</a> and related molecules</td> <td>inhibit cell proliferation and induce <a href="/wiki/Apoptosis" title="Apoptosis">apoptosis</a> of endothelial cells </td></tr> <tr> <td><a href="/wiki/Endostatin" title="Endostatin">endostatin</a></td> <td>inhibit cell migration, cell proliferation and survival of endothelial cells </td></tr> <tr> <td><a href="/wiki/Vasostatin" class="mw-redirect" title="Vasostatin">vasostatin</a>, <a href="/wiki/Calreticulin" title="Calreticulin">calreticulin</a></td> <td>inhibit cell proliferation of endothelial cells </td></tr> <tr> <td><a href="/wiki/Platelet_factor-4" class="mw-redirect" title="Platelet factor-4">platelet factor-4</a></td> <td>inhibits binding of <a href="/wiki/BFGF" class="mw-redirect" title="BFGF">bFGF</a> and <a href="/wiki/Vascular_endothelial_growth_factor" title="Vascular endothelial growth factor">VEGF</a> </td></tr> <tr> <td><a href="/wiki/Tissue_inhibitor_of_metalloproteinases" class="mw-redirect" title="Tissue inhibitor of metalloproteinases">TIMP</a> and <a href="/wiki/Cartilage-derived_angiogenesis_inhibitor" title="Cartilage-derived angiogenesis inhibitor">CDAI</a></td> <td>inhibit cell migration of endothelial cells </td></tr> <tr> <td><a href="/wiki/ADAMTS1" title="ADAMTS1">ADAMTS1</a> and <a href="/wiki/ADAMTS8" title="ADAMTS8">ADAMTS8</a></td> <td> </td></tr> <tr> <td><a href="/wiki/Interferon_alpha" class="mw-redirect" title="Interferon alpha">IFN-α</a>, <a href="/wiki/Interferon_beta" class="mw-redirect" title="Interferon beta">-β</a> and <a href="/wiki/Interferon_gamma" title="Interferon gamma">-γ</a>, <a href="/wiki/CXCL10" title="CXCL10">CXCL10</a>, <a href="/wiki/Interleukin_4" title="Interleukin 4">IL-4</a>, <a href="/wiki/Interleukin_12" title="Interleukin 12">-12</a> and <a href="/wiki/Interleukin_18" title="Interleukin 18">-18</a></td> <td>inhibit cell migration of endothelial cells, downregulate bFGF </td></tr> <tr> <td><a href="/wiki/Prothrombin" class="mw-redirect" title="Prothrombin">prothrombin</a> (<a href="/wiki/Kringle_domain" title="Kringle domain">kringle domain</a>-2), <a href="/wiki/Antithrombin_III" class="mw-redirect" title="Antithrombin III">antithrombin III</a> fragment</td> <td>inhibit cell proliferation of endothelial cells </td></tr> <tr> <td><a href="/wiki/Prolactin" title="Prolactin">prolactin</a></td> <td>VEGF </td></tr> <tr> <td><a href="/wiki/VEGI" class="mw-redirect" title="VEGI">VEGI</a></td> <td>affects cell proliferation of endothelial cells </td></tr> <tr> <td>SPARC</td> <td>inhibit binding and activity of <a href="/wiki/Vascular_endothelial_growth_factor" title="Vascular endothelial growth factor">VEGF</a> </td></tr> <tr> <td><a href="/wiki/Osteopontin" title="Osteopontin">osteopontin</a></td> <td>inhibit <a href="/wiki/Integrin" title="Integrin">integrin</a> signalling </td></tr> <tr> <td><a href="/wiki/Maspin" title="Maspin">maspin</a></td> <td>inhibits <a href="/wiki/Proteases" class="mw-redirect" title="Proteases">proteases</a> </td></tr> <tr> <td>canstatin (a fragment of <a href="/wiki/COL4A2" class="mw-redirect" title="COL4A2">COL4A2</a>)</td> <td>inhibits endothelial cell migration, induces apoptosis<sup id="cite_ref-Kamphaus-2000_16-0" class="reference"><a href="#cite_note-Kamphaus-2000-16"><span class="cite-bracket">[</span>16<span class="cite-bracket">]</span></a></sup> </td></tr> <tr> <td>proliferin-related protein</td> <td><a href="/wiki/Mannose_6-phosphate" title="Mannose 6-phosphate">mannose 6-phosphate</a> binding lysosomal protein<sup id="cite_ref-Lee-1988_17-0" class="reference"><a href="#cite_note-Lee-1988-17"><span class="cite-bracket">[</span>17<span class="cite-bracket">]</span></a></sup> </td></tr> </tbody></table> <p>A recent method for the delivery of anti-angiogenesis factors to tumor regions in cancer patients uses <a href="/wiki/Genetically_modified_bacterium" class="mw-redirect" title="Genetically modified bacterium">genetically modified bacteria</a> that are able to colonize solid tumors <i>in vivo</i>, such as <i><a href="/wiki/Clostridium" title="Clostridium">Clostridium</a></i>, <i><a href="/wiki/Bifidobacteria" class="mw-redirect" title="Bifidobacteria">Bifidobacteria</a></i> and <i><a href="/wiki/Salmonella" title="Salmonella">Salmonella</a></i> by adding genes for anti-angiogenic factors such as <a href="/wiki/Endostatin" title="Endostatin">endostatin</a> or IP10 <a href="/wiki/Chemokine" title="Chemokine">chemokine</a> and removing any harmful virulence genes. A target can also be added to the outside of the bacteria so that they are sent to the correct organ in the body. The bacteria can then be injected into the patient and they will locate themselves to the tumor site, where they release a continual supply of the desired drugs in the vicinity of a growing cancer mass, preventing it from being able to gain access to oxygen and ultimately starving the cancer cells.<sup id="cite_ref-18" class="reference"><a href="#cite_note-18"><span class="cite-bracket">[</span>18<span class="cite-bracket">]</span></a></sup> This method has been shown to work both in vitro and in vivo in mice models, with very promising results.<sup id="cite_ref-19" class="reference"><a href="#cite_note-19"><span class="cite-bracket">[</span>19<span class="cite-bracket">]</span></a></sup> It is expected that this method will become commonplace for treatment of various cancer types in humans in the future.<sup class="noprint Inline-Template Template-Fact" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed"><span title="This claim needs references to reliable sources. (May 2020)">citation needed</span></a></i>]</sup> </p> <div class="mw-heading mw-heading2"><h2 id="Exogenous_regulation">Exogenous regulation</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Angiogenesis_inhibitor&action=edit&section=4" title="Edit section: Exogenous regulation"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <div class="mw-heading mw-heading3"><h3 id="Diet">Diet</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Angiogenesis_inhibitor&action=edit&section=5" title="Edit section: Diet"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Some common components of human diets also act as mild angiogenesis inhibitors and have therefore been proposed for <a href="/wiki/Angioprevention" title="Angioprevention">angioprevention</a>, the prevention of <a href="/wiki/Metastasis" title="Metastasis">metastasis</a> through the inhibition of <a href="/wiki/Angiogenesis" title="Angiogenesis">angiogenesis</a>. In particular, the following foods contain significant inhibitors and have been suggested as part of a healthy diet for this and other benefits: </p> <ul><li><a href="/wiki/Soy_products" class="mw-redirect" title="Soy products">Soy products</a> such as <a href="/wiki/Tofu" title="Tofu">tofu</a> and <a href="/wiki/Tempeh" title="Tempeh">tempeh</a>, (which contain the inhibitor "<a href="/wiki/Genistein" title="Genistein">genistein</a>")<sup id="cite_ref-20" class="reference"><a href="#cite_note-20"><span class="cite-bracket">[</span>20<span class="cite-bracket">]</span></a></sup></li> <li><i><a href="/wiki/Agaricus_subrufescens" title="Agaricus subrufescens">Agaricus subrufescens</a></i> mushrooms (contain the inhibitors <a href="/wiki/Pyroglutamic_acid" title="Pyroglutamic acid">sodium pyroglutamate</a> and <a href="/wiki/Ergosterol" title="Ergosterol">ergosterol</a>)<sup id="cite_ref-Isolation_of_an_anti-angiogenic_substance_from_Agaricus_blazei_Murill:_its_antitumor_and_antimetastatic_actions._21-0" class="reference"><a href="#cite_note-Isolation_of_an_anti-angiogenic_substance_from_Agaricus_blazei_Murill:_its_antitumor_and_antimetastatic_actions.-21"><span class="cite-bracket">[</span>21<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid11340091_22-0" class="reference"><a href="#cite_note-pmid11340091-22"><span class="cite-bracket">[</span>22<span class="cite-bracket">]</span></a></sup></li> <li><a href="/wiki/Rubus_occidentalis" title="Rubus occidentalis">Black raspberry</a> (<i>Rubus occidentalis</i>) extract<sup id="cite_ref-23" class="reference"><a href="#cite_note-23"><span class="cite-bracket">[</span>23<span class="cite-bracket">]</span></a></sup></li> <li><a href="/wiki/Lingzhi_mushroom" class="mw-redirect" title="Lingzhi mushroom">Lingzhi mushrooms</a> (via inhibition of <a href="/wiki/Vascular_endothelial_growth_factor" title="Vascular endothelial growth factor">VEGF</a> and <a href="/wiki/TGF-beta" class="mw-redirect" title="TGF-beta">TGF-beta</a>)<sup id="cite_ref-pmid15781230_24-0" class="reference"><a href="#cite_note-pmid15781230-24"><span class="cite-bracket">[</span>24<span class="cite-bracket">]</span></a></sup></li> <li><i><a href="/wiki/Trametes_versicolor" title="Trametes versicolor">Trametes versicolor</a></i> mushrooms (<a href="/wiki/Polysaccharide-K" title="Polysaccharide-K">Polysaccharide-K</a>)<sup id="cite_ref-pmid2743504_25-0" class="reference"><a href="#cite_note-pmid2743504-25"><span class="cite-bracket">[</span>25<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid17106715_26-0" class="reference"><a href="#cite_note-pmid17106715-26"><span class="cite-bracket">[</span>26<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid9219507_27-0" class="reference"><a href="#cite_note-pmid9219507-27"><span class="cite-bracket">[</span>27<span class="cite-bracket">]</span></a></sup></li> <li><i><a href="/wiki/Maitake" class="mw-redirect" title="Maitake">Maitake</a></i> mushrooms (via inhibition of <a href="/wiki/Vascular_endothelial_growth_factor" title="Vascular endothelial growth factor">VEGF</a>)<sup id="cite_ref-28" class="reference"><a href="#cite_note-28"><span class="cite-bracket">[</span>28<span class="cite-bracket">]</span></a></sup></li> <li><i><a href="/wiki/Phellinus_linteus" class="mw-redirect" title="Phellinus linteus">Phellinus linteus</a></i> mushrooms<sup id="cite_ref-29" class="reference"><a href="#cite_note-29"><span class="cite-bracket">[</span>29<span class="cite-bracket">]</span></a></sup> (via active substance Interfungins A inhibition of <a href="/wiki/Glycation" title="Glycation">glycation</a>)<sup id="cite_ref-pmid18827365_30-0" class="reference"><a href="#cite_note-pmid18827365-30"><span class="cite-bracket">[</span>30<span class="cite-bracket">]</span></a></sup></li> <li><a href="/wiki/Green_tea" title="Green tea">Green tea</a> (<a href="/wiki/Tea_catechins" class="mw-redirect" title="Tea catechins">catechins</a>)<sup id="cite_ref-31" class="reference"><a href="#cite_note-31"><span class="cite-bracket">[</span>31<span class="cite-bracket">]</span></a></sup></li> <li><a href="/wiki/Liquorice" title="Liquorice">Liquorice</a> (<a href="/wiki/Glycyrrhizic_acid" class="mw-redirect" title="Glycyrrhizic acid">glycyrrhizic acid</a>)<sup id="cite_ref-antiangio_32-0" class="reference"><a href="#cite_note-antiangio-32"><span class="cite-bracket">[</span>32<span class="cite-bracket">]</span></a></sup></li> <li><a href="/wiki/Red_wine" title="Red wine">Red wine</a> (<a href="/wiki/Resveratrol" title="Resveratrol">resveratrol</a>)<sup id="cite_ref-antiangio_32-1" class="reference"><a href="#cite_note-antiangio-32"><span class="cite-bracket">[</span>32<span class="cite-bracket">]</span></a></sup></li> <li>Antiangiogenic <a href="/wiki/Phytochemical" title="Phytochemical">phytochemicals</a> and medicinal herbs<sup id="cite_ref-33" class="reference"><a href="#cite_note-33"><span class="cite-bracket">[</span>33<span class="cite-bracket">]</span></a></sup></li> <li><a href="/wiki/Royal_Jelly" class="mw-redirect" title="Royal Jelly">Royal Jelly</a> (<a href="/wiki/Queen_bee_acid" title="Queen bee acid">Queen bee acid</a>)<sup id="cite_ref-34" class="reference"><a href="#cite_note-34"><span class="cite-bracket">[</span>34<span class="cite-bracket">]</span></a></sup></li></ul> <div class="mw-heading mw-heading3"><h3 id="Drugs">Drugs</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Angiogenesis_inhibitor&action=edit&section=6" title="Edit section: Drugs"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Research and development in this field has been driven largely by the desire to find better cancer treatments. Tumors cannot grow larger than 2mm without angiogenesis. By stopping the growth of blood vessels, scientists hope to cut the means by which tumors can nourish themselves and thus <a href="/wiki/Metastasize" class="mw-redirect" title="Metastasize">metastasize</a>. </p><p>In addition to their use as anti-cancer drugs, angiogenesis inhibitors are being investigated for their use as <a href="/wiki/Anti-obesity" class="mw-redirect" title="Anti-obesity">anti-obesity</a> agents, as blood vessels in <a href="/wiki/Adipose_tissue" title="Adipose tissue">adipose tissue</a> never fully mature, and are thus destroyed by angiogenesis inhibitors.<sup id="cite_ref-Bruemmer2012_35-0" class="reference"><a href="#cite_note-Bruemmer2012-35"><span class="cite-bracket">[</span>35<span class="cite-bracket">]</span></a></sup> Angiogenesis inhibitors are also used as treatment for the wet form of macular degeneration. By blocking VEGF, inhibitors can cause regression of the abnormal blood vessels in the retina and improve vision when injected directly into the <a href="/wiki/Vitreous_humor" class="mw-redirect" title="Vitreous humor">vitreous humor</a> of the eye.<sup id="cite_ref-36" class="reference"><a href="#cite_note-36"><span class="cite-bracket">[</span>36<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading4"><h4 id="Overview">Overview</h4><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Angiogenesis_inhibitor&action=edit&section=7" title="Edit section: Overview"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <table class="wikitable"> <tbody><tr> <th>Inhibitors</th> <th>Mechanism </th></tr> <tr> <td><a href="/wiki/Bevacizumab" title="Bevacizumab">bevacizumab</a> (Avastin)</td> <td>VEGF </td></tr> <tr> <td><a href="/wiki/Itraconazole" title="Itraconazole">itraconazole</a></td> <td>inhibits <a href="/wiki/VEGFR" class="mw-redirect" title="VEGFR">VEGFR</a> phosphorylation, <a href="/wiki/Glycosylation" title="Glycosylation">glycosylation</a>, <a href="/wiki/MTOR" title="MTOR">mTOR</a> signaling, endothelial cell proliferation, cell migration, <a href="/wiki/Lumen_(anatomy)" title="Lumen (anatomy)">lumen</a> formation, and tumor associated angiogenesis.<sup id="cite_ref-Chong_37-0" class="reference"><a href="#cite_note-Chong-37"><span class="cite-bracket">[</span>37<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Aftab_38-0" class="reference"><a href="#cite_note-Aftab-38"><span class="cite-bracket">[</span>38<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-39" class="reference"><a href="#cite_note-39"><span class="cite-bracket">[</span>39<span class="cite-bracket">]</span></a></sup> </td></tr> <tr> <td><a href="/wiki/Carboxyamidotriazole" title="Carboxyamidotriazole">carboxyamidotriazole</a></td> <td rowspan="2"><a href="/wiki/METAP2" title="METAP2">Methionine aminopeptidase 2</a> inhibitors,<sup id="cite_ref-40" class="reference"><a href="#cite_note-40"><span class="cite-bracket">[</span>40<span class="cite-bracket">]</span></a></sup> inhibit cell proliferation and cell migration of endothelial cells </td></tr> <tr> <td><a href="/wiki/TNP-470" title="TNP-470">TNP-470</a> (an analog of <a href="/wiki/Fumagillin" title="Fumagillin">fumagillin</a>) </td></tr> <tr> <td>CM101</td> <td>activate <a href="/wiki/Immune_system" title="Immune system">immune system</a> </td></tr> <tr> <td><a href="/wiki/Interferon_alpha" class="mw-redirect" title="Interferon alpha">IFN-α</a></td> <td>downregulate angiogenesis stimulators and inhibit cell migration of endothelial cells </td></tr> <tr> <td><a href="/wiki/Interleukin_12" title="Interleukin 12">IL-12</a></td> <td>stimulate angiogenesis inhibitor formation </td></tr> <tr> <td><a href="/wiki/Platelet_factor-4" class="mw-redirect" title="Platelet factor-4">platelet factor-4</a></td> <td rowspan="5">inhibits binding of angiogenesis stimulators </td></tr> <tr> <td><a href="/wiki/Suramin" title="Suramin">suramin</a> </td></tr> <tr> <td><a href="/wiki/SU5416" class="mw-redirect" title="SU5416">SU5416</a> </td></tr> <tr> <td><a href="/wiki/Thrombospondin" title="Thrombospondin">thrombospondin</a> </td></tr> <tr> <td>VEGFR antagonists </td></tr> <tr> <td>angiostatic steroids + <a href="/wiki/Heparin" title="Heparin">heparin</a></td> <td rowspan="3">inhibit <a href="/wiki/Basement_membrane" title="Basement membrane">basement membrane</a> degradation </td></tr> <tr> <td><a href="/wiki/Cartilage-Derived_Angiogenesis_Inhibitory_Factor" class="mw-redirect" title="Cartilage-Derived Angiogenesis Inhibitory Factor">Cartilage-Derived Angiogenesis Inhibitory Factor</a> </td></tr> <tr> <td><a href="/wiki/Matrix_metalloproteinase_inhibitor" title="Matrix metalloproteinase inhibitor">matrix metalloproteinase inhibitors</a> </td></tr> <tr> <td><a href="/wiki/Angiostatin" title="Angiostatin">angiostatin</a></td> <td>inhibit cell proliferation and induce apoptosis of endothelial cells </td></tr> <tr> <td><a href="/wiki/Endostatin" title="Endostatin">endostatin</a></td> <td>inhibit cell migration, cell proliferation and survival of endothelial cells </td></tr> <tr> <td><a href="/wiki/2-methoxyestradiol" class="mw-redirect" title="2-methoxyestradiol">2-methoxyestradiol</a></td> <td>inhibit cell proliferation and cell migration and induce apoptosis of endothelial cells </td></tr> <tr> <td>tecogalan</td> <td>inhibit cell proliferation of endothelial cells </td></tr> <tr> <td><a href="/wiki/Tetrathiomolybdate" title="Tetrathiomolybdate">tetrathiomolybdate</a></td> <td>copper chelation which inhibits blood vessel growth </td></tr> <tr> <td><a href="/wiki/Thalidomide" title="Thalidomide">thalidomide</a></td> <td>inhibit cell proliferation of endothelial cells </td></tr> <tr> <td><a href="/wiki/Thrombospondin" title="Thrombospondin">thrombospondin</a></td> <td>inhibit cell migration, cell proliferation, cell adhesion and survival of endothelial cells </td></tr> <tr> <td><a href="/wiki/Prolactin" title="Prolactin">prolactin</a></td> <td>VEGF </td></tr> <tr> <td><a href="/wiki/Alpha-V_beta-3" class="mw-redirect" title="Alpha-V beta-3">α<sub>V</sub>β<sub>3</sub></a> inhibitors</td> <td>induce apoptosis of endothelial cells </td></tr> <tr> <td><a href="/wiki/Roquinimex" class="mw-redirect" title="Roquinimex">linomide</a></td> <td>inhibit cell migration of endothelial cells </td></tr> <tr> <td><a href="/wiki/Ramucirumab" title="Ramucirumab">ramucirumab</a> </td> <td>inhibition of VEGFR<sub>2</sub><sup id="cite_ref-41" class="reference"><a href="#cite_note-41"><span class="cite-bracket">[</span>41<span class="cite-bracket">]</span></a></sup> </td></tr> <tr> <td><a href="/wiki/Tasquinimod" title="Tasquinimod">tasquinimod</a></td> <td><i>Unknown</i><sup id="cite_ref-RH2011_42-0" class="reference"><a href="#cite_note-RH2011-42"><span class="cite-bracket">[</span>42<span class="cite-bracket">]</span></a></sup> </td></tr> <tr> <td><a href="/wiki/Ranibizumab" title="Ranibizumab">ranibizumab</a></td> <td>VEGF<sup id="cite_ref-RosenfeldBrown2006_43-0" class="reference"><a href="#cite_note-RosenfeldBrown2006-43"><span class="cite-bracket">[</span>43<span class="cite-bracket">]</span></a></sup> </td></tr> <tr> <td><a href="/wiki/Sorafenib" title="Sorafenib">sorafenib</a> (Nexavar)</td> <td rowspan="4">inhibit kinases </td></tr> <tr> <td><a href="/wiki/Sunitinib" title="Sunitinib">sunitinib</a> (Sutent)</td> <td> </td></tr> <tr> <td><a href="/wiki/Pazopanib" title="Pazopanib">pazopanib</a> (Votrient)</td> <td> </td></tr> <tr> <td><a href="/wiki/Everolimus" title="Everolimus">everolimus</a> (Afinitor)</td> <td> </td></tr></tbody></table> <figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:Angiogenesis_Inhibitors_Image.tiff" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/8/81/Angiogenesis_Inhibitors_Image.tiff/lossy-page1-220px-Angiogenesis_Inhibitors_Image.tiff.jpg" decoding="async" width="220" height="197" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/8/81/Angiogenesis_Inhibitors_Image.tiff/lossy-page1-330px-Angiogenesis_Inhibitors_Image.tiff.jpg 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/8/81/Angiogenesis_Inhibitors_Image.tiff/lossy-page1-440px-Angiogenesis_Inhibitors_Image.tiff.jpg 2x" data-file-width="1050" data-file-height="938" /></a><figcaption>Mechanism of action of angiogenesis inhibitors. Bevacizumab binds to VEGF inhibiting its ability to bind to and activate VEGF receptors. Sunitinib and Sorafenib inhibit VEGF receptors. Sorafenib also acts downstream.</figcaption></figure> <div class="mw-heading mw-heading4"><h4 id="Bevacizumab">Bevacizumab</h4><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Angiogenesis_inhibitor&action=edit&section=8" title="Edit section: Bevacizumab"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Through binding to <a href="/wiki/VEGFR" class="mw-redirect" title="VEGFR">VEGFR</a> and other VEGF receptors in endothelial cells, VEGF can trigger multiple cellular responses like promoting cell survival, preventing apoptosis, and remodeling <a href="/wiki/Cytoskeleton" title="Cytoskeleton">cytoskeleton</a>, all of which promote angiogenesis. Bevacizumab (brand name Avastin) traps VEGF in the blood, lowering the binding of VEGF to its receptors. This results in reduced activation of the angiogenesis pathway, thus inhibiting new blood vessel formation in tumors.<sup id="cite_ref-Nyberg_P,_Xie_L,_Kalluri_R_3967–79_14-2" class="reference"><a href="#cite_note-Nyberg_P,_Xie_L,_Kalluri_R_3967–79-14"><span class="cite-bracket">[</span>14<span class="cite-bracket">]</span></a></sup> </p><p>After a series of <a href="/wiki/Clinical_trials" class="mw-redirect" title="Clinical trials">clinical trials</a> in 2004, <a href="/wiki/Avastin" class="mw-redirect" title="Avastin">Avastin</a> was approved by the FDA, becoming the first commercially available anti-angiogenesis drug. FDA approval of Avastin for breast cancer treatment was later revoked on November 18, 2011.<sup id="cite_ref-44" class="reference"><a href="#cite_note-44"><span class="cite-bracket">[</span>44<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading4"><h4 id="Thalidomide">Thalidomide</h4><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Angiogenesis_inhibitor&action=edit&section=9" title="Edit section: Thalidomide"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Despite the therapeutic potential of anti-angiogenesis drugs, they can also be harmful when used inappropriately. <a href="/wiki/Thalidomide" title="Thalidomide">Thalidomide</a> is one such antiangiogenic agent. Thalidomide was given to pregnant women to treat nausea. However, when pregnant women take an antiangiogenic agent, the developing fetus will not form blood vessels properly, thereby preventing the proper development of fetal limbs and circulatory systems. In the late 1950s and early 1960s, thousands of children were born with <a href="/wiki/Deformities" class="mw-redirect" title="Deformities">deformities</a>, most notably <a href="/wiki/Phocomelia" title="Phocomelia">phocomelia</a>, as a consequence of thalidomide use.<sup id="cite_ref-KimScialli2011_45-0" class="reference"><a href="#cite_note-KimScialli2011-45"><span class="cite-bracket">[</span>45<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading4"><h4 id="Cannabinoids">Cannabinoids</h4><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Angiogenesis_inhibitor&action=edit&section=10" title="Edit section: Cannabinoids"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>According to a study published in the August 15, 2004 issue of the journal <i>Cancer Research</i>, <a href="/wiki/Cannabinoids" class="mw-redirect" title="Cannabinoids">cannabinoids</a>, the active ingredients in <a href="/wiki/Marijuana" class="mw-redirect" title="Marijuana">marijuana</a>, restrict the sprouting of blood vessels to gliomas (brain tumors) implanted under the skin of mice, by inhibiting the expression of genes needed for the production of vascular endothelial growth factor (VEGF).<sup id="cite_ref-46" class="reference"><a href="#cite_note-46"><span class="cite-bracket">[</span>46<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="General_side_effects_of_drugs">General side effects of drugs</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Angiogenesis_inhibitor&action=edit&section=11" title="Edit section: General side effects of drugs"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <div class="mw-heading mw-heading4"><h4 id="Bleeding">Bleeding</h4><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Angiogenesis_inhibitor&action=edit&section=12" title="Edit section: Bleeding"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Bleeding is one of the most difficult side effects to manage; this complication is somewhat inherent to the effectiveness of the drug. Bevacizumab has been shown to be the drug most likely to cause bleeding complications. <sup class="noprint Inline-Template Template-Fact" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed"><span title="This claim needs references to reliable sources. (May 2020)">citation needed</span></a></i>]</sup> While the mechanisms of bleeding induced by anti-VEGF agents are complicated and not yet totally understood, the most accepted hypothesis is that VEGF could promote endothelial cell survival and integrity in the adult vasculature and its inhibition may decrease capacity for renewal of damaged endothelial cells.<sup id="cite_ref-Elice_47-0" class="reference"><a href="#cite_note-Elice-47"><span class="cite-bracket">[</span>47<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading4"><h4 id="Increased_blood_pressure">Increased blood pressure</h4><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Angiogenesis_inhibitor&action=edit&section=13" title="Edit section: Increased blood pressure"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>In a study done by ML Maitland, a mean blood pressure increase of 8.2 mm Hg systolic and 6.5 mm Hg diastolic was reported in the first 24 hours after the first treatment with sorafenib, a VEGF pathway inhibitor.<sup id="cite_ref-48" class="reference"><a href="#cite_note-48"><span class="cite-bracket">[</span>48<span class="cite-bracket">]</span></a></sup><sup class="noprint Inline-Template noprint Template-Fact" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:No_original_research#Primary,_secondary_and_tertiary_sources" title="Wikipedia:No original research"><span title="This claim needs references to reliable secondary sources. (May 2014)">non-primary source needed</span></a></i>]</sup> </p> <div class="mw-heading mw-heading4"><h4 id="Less_common_side_effects">Less common side effects</h4><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Angiogenesis_inhibitor&action=edit&section=14" title="Edit section: Less common side effects"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Because these drugs act on parts of the blood and blood vessels, they tend to have side effects that affect these processes. Aside from problems with hemorrhage and hypertension, less common side effects of these drugs include dry, itchy skin, hand-foot syndrome (tender, thickened areas on the skin, sometimes with blisters on palms and soles), diarrhea, fatigue, and low blood counts. Angiogenesis inhibitors can also interfere with wound healing and cause cuts to re-open or bleed. Rarely, perforations (holes) in the intestines can occur.<sup id="cite_ref-Elice_47-1" class="reference"><a href="#cite_note-Elice-47"><span class="cite-bracket">[</span>47<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="See_also">See also</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Angiogenesis_inhibitor&action=edit&section=15" title="Edit section: See also"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <ul><li><a href="/wiki/Brain-specific_angiogenesis_inhibitor_1" title="Brain-specific angiogenesis inhibitor 1">Brain-specific angiogenesis inhibitor 1</a> (and others)</li></ul> <div class="mw-heading mw-heading2"><h2 id="References">References</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Angiogenesis_inhibitor&action=edit&section=16" title="Edit section: References"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <style data-mw-deduplicate="TemplateStyles:r1239543626">.mw-parser-output .reflist{margin-bottom:0.5em;list-style-type:decimal}@media screen{.mw-parser-output .reflist{font-size:90%}}.mw-parser-output .reflist .references{font-size:100%;margin-bottom:0;list-style-type:inherit}.mw-parser-output .reflist-columns-2{column-width:30em}.mw-parser-output .reflist-columns-3{column-width:25em}.mw-parser-output .reflist-columns{margin-top:0.3em}.mw-parser-output .reflist-columns ol{margin-top:0}.mw-parser-output .reflist-columns li{page-break-inside:avoid;break-inside:avoid-column}.mw-parser-output .reflist-upper-alpha{list-style-type:upper-alpha}.mw-parser-output .reflist-upper-roman{list-style-type:upper-roman}.mw-parser-output .reflist-lower-alpha{list-style-type:lower-alpha}.mw-parser-output .reflist-lower-greek{list-style-type:lower-greek}.mw-parser-output .reflist-lower-roman{list-style-type:lower-roman}</style><div class="reflist"> <div class="mw-references-wrap mw-references-columns"><ol class="references"> <li id="cite_note-1"><span class="mw-cite-backlink"><b><a href="#cite_ref-1">^</a></b></span> <span class="reference-text"><style data-mw-deduplicate="TemplateStyles:r1238218222">.mw-parser-output cite.citation{font-style:inherit;word-wrap:break-word}.mw-parser-output .citation q{quotes:"\"""\"""'""'"}.mw-parser-output .citation:target{background-color:rgba(0,127,255,0.133)}.mw-parser-output .id-lock-free.id-lock-free a{background:url("//upload.wikimedia.org/wikipedia/commons/6/65/Lock-green.svg")right 0.1em center/9px no-repeat}.mw-parser-output .id-lock-limited.id-lock-limited a,.mw-parser-output .id-lock-registration.id-lock-registration a{background:url("//upload.wikimedia.org/wikipedia/commons/d/d6/Lock-gray-alt-2.svg")right 0.1em center/9px no-repeat}.mw-parser-output .id-lock-subscription.id-lock-subscription a{background:url("//upload.wikimedia.org/wikipedia/commons/a/aa/Lock-red-alt-2.svg")right 0.1em center/9px no-repeat}.mw-parser-output .cs1-ws-icon a{background:url("//upload.wikimedia.org/wikipedia/commons/4/4c/Wikisource-logo.svg")right 0.1em center/12px no-repeat}body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-free a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-limited a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-registration a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-subscription a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .cs1-ws-icon a{background-size:contain;padding:0 1em 0 0}.mw-parser-output .cs1-code{color:inherit;background:inherit;border:none;padding:inherit}.mw-parser-output .cs1-hidden-error{display:none;color:var(--color-error,#d33)}.mw-parser-output .cs1-visible-error{color:var(--color-error,#d33)}.mw-parser-output .cs1-maint{display:none;color:#085;margin-left:0.3em}.mw-parser-output .cs1-kern-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right{padding-right:0.2em}.mw-parser-output .citation .mw-selflink{font-weight:inherit}@media screen{.mw-parser-output .cs1-format{font-size:95%}html.skin-theme-clientpref-night .mw-parser-output .cs1-maint{color:#18911f}}@media screen and (prefers-color-scheme:dark){html.skin-theme-clientpref-os .mw-parser-output .cs1-maint{color:#18911f}}</style><cite id="CITEREFHayden2009" class="citation journal cs1">Hayden EC (April 2009). <a rel="nofollow" class="external text" href="https://doi.org/10.1038%2F458686b">"Cutting off cancer's supply lines"</a>. <i>Nature</i>. <b>458</b> (7239): 686–7. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://doi.org/10.1038%2F458686b">10.1038/458686b</a></span>. <a 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"Cannabinoids inhibit the vascular endothelial growth factor pathway in gliomas". <i>Cancer Research</i>. <b>64</b> (16): 5617–23. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1158%2F0008-5472.CAN-03-3927">10.1158/0008-5472.CAN-03-3927</a>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/15313899">15313899</a>. <a href="/wiki/S2CID_(identifier)" class="mw-redirect" title="S2CID (identifier)">S2CID</a> <a rel="nofollow" class="external text" href="https://api.semanticscholar.org/CorpusID:1357974">1357974</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Cancer+Research&rft.atitle=Cannabinoids+inhibit+the+vascular+endothelial+growth+factor+pathway+in+gliomas&rft.volume=64&rft.issue=16&rft.pages=5617-23&rft.date=2004-08&rft_id=https%3A%2F%2Fapi.semanticscholar.org%2FCorpusID%3A1357974%23id-name%3DS2CID&rft_id=info%3Apmid%2F15313899&rft_id=info%3Adoi%2F10.1158%2F0008-5472.CAN-03-3927&rft.aulast=Bl%C3%A1zquez&rft.aufirst=C&rft.au=Gonz%C3%A1lez-Feria%2C+L&rft.au=Alvarez%2C+L&rft.au=Haro%2C+A&rft.au=Casanova%2C+ML&rft.au=Guzm%C3%A1n%2C+M&rfr_id=info%3Asid%2Fen.wikipedia.org%3AAngiogenesis+inhibitor" class="Z3988"></span></span> </li> <li id="cite_note-Elice-47"><span class="mw-cite-backlink">^ <a href="#cite_ref-Elice_47-0"><sup><i><b>a</b></i></sup></a> <a href="#cite_ref-Elice_47-1"><sup><i><b>b</b></i></sup></a></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFEliceRodeghiero2012" class="citation journal cs1">Elice F, Rodeghiero F (April 2012). "Side effects of anti-angiogenic drugs". <i>Thrombosis Research</i>. <b>129</b>: S50–3. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1016%2FS0049-3848%2812%2970016-6">10.1016/S0049-3848(12)70016-6</a>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/22682133">22682133</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Thrombosis+Research&rft.atitle=Side+effects+of+anti-angiogenic+drugs&rft.volume=129&rft.pages=S50-3&rft.date=2012-04&rft_id=info%3Adoi%2F10.1016%2FS0049-3848%2812%2970016-6&rft_id=info%3Apmid%2F22682133&rft.aulast=Elice&rft.aufirst=F&rft.au=Rodeghiero%2C+F&rfr_id=info%3Asid%2Fen.wikipedia.org%3AAngiogenesis+inhibitor" class="Z3988"></span></span> </li> <li id="cite_note-48"><span class="mw-cite-backlink"><b><a href="#cite_ref-48">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFMaitlandKaszaKarrisonMoshier2009" class="citation journal cs1">Maitland ML, Kasza KE, Karrison T, Moshier K, Sit L, Black HR, Undevia SD, Stadler WM, Elliott WJ, Ratain MJ (October 2009). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2756980">"Ambulatory monitoring detects sorafenib-induced blood pressure elevations on the first day of treatment"</a>. <i>Clinical Cancer Research</i>. <b>15</b> (19): 6250–7. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1158%2F1078-0432.CCR-09-0058">10.1158/1078-0432.CCR-09-0058</a>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2756980">2756980</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/19773379">19773379</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Clinical+Cancer+Research&rft.atitle=Ambulatory+monitoring+detects+sorafenib-induced+blood+pressure+elevations+on+the+first+day+of+treatment&rft.volume=15&rft.issue=19&rft.pages=6250-7&rft.date=2009-10&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC2756980%23id-name%3DPMC&rft_id=info%3Apmid%2F19773379&rft_id=info%3Adoi%2F10.1158%2F1078-0432.CCR-09-0058&rft.aulast=Maitland&rft.aufirst=ML&rft.au=Kasza%2C+KE&rft.au=Karrison%2C+T&rft.au=Moshier%2C+K&rft.au=Sit%2C+L&rft.au=Black%2C+HR&rft.au=Undevia%2C+SD&rft.au=Stadler%2C+WM&rft.au=Elliott%2C+WJ&rft.au=Ratain%2C+MJ&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC2756980&rfr_id=info%3Asid%2Fen.wikipedia.org%3AAngiogenesis+inhibitor" class="Z3988"></span></span> </li> </ol></div></div> <div class="mw-heading mw-heading2"><h2 id="Further_reading">Further reading</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Angiogenesis_inhibitor&action=edit&section=17" title="Edit section: Further reading"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <ul><li>Milosevic, V., Edelmann, R.J., Fosse, J.H., Östman, A., Akslen, L.A. (2022). <a rel="nofollow" class="external text" href="https://link.springer.com/chapter/10.1007/978-3-030-98950-7_3">Molecular Phenotypes of Endothelial Cells in Malignant Tumors. In: Akslen, L.A., Watnick, R.S. (eds) Biomarkers of the Tumor Microenvironment</a>. Springer, Cham. <a rel="nofollow" class="external free" href="https://doi.org/10.1007/978-3-030-98950-7_3">https://doi.org/10.1007/978-3-030-98950-7_3</a></li></ul> <div class="mw-heading mw-heading2"><h2 id="External_links">External links</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Angiogenesis_inhibitor&action=edit&section=18" title="Edit section: External links"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <ul><li>The idea of antiangiogenesis was pioneered by Dr. Judah Folkman. See <a rel="nofollow" class="external autonumber" href="https://www.pbs.org/wgbh/nova/cancer/trials.html">[1]</a> and <a rel="nofollow" class="external autonumber" href="https://www.pbs.org/wgbh/nova/body/judah-folkman.html">[2]</a></li> <li><a rel="nofollow" class="external text" href="https://web.archive.org/web/20090811005903/http://www.angio.org/understanding/inhib.php">Angiogenesis Inhibitors for Cancer</a> - from <a rel="nofollow" class="external text" href="http://www.angio.org">The Angiogenesis Foundation</a>, 23 June 2009</li> <li><a rel="nofollow" class="external text" href="https://web.archive.org/web/20090811005923/http://www.angio.org/understanding/inhibeye.php">Angiogenesis Inhibitors for Eye Disease</a> - from <a rel="nofollow" class="external text" href="http://www.angio.org">The Angiogenesis Foundation</a>, 23 June 2009</li> <li><a rel="nofollow" class="external text" href="https://www.cancer.gov/cancertopics/factsheet/Therapy/angiogenesis-inhibitors">Angiogenesis Inhibitors in the Treatment of Cancer</a> - from the <a href="/wiki/National_Cancer_Institute" title="National Cancer Institute">National Cancer Institute</a></li> <li><a rel="nofollow" class="external text" href="https://meshb.nlm.nih.gov/record/ui?name=Angiogenesis+Inhibitors">Angiogenesis+Inhibitors</a> at the U.S. National Library of Medicine <a href="/wiki/Medical_Subject_Headings" title="Medical Subject Headings">Medical Subject Headings</a> (MeSH)</li></ul> <div class="navbox-styles"><style data-mw-deduplicate="TemplateStyles:r1129693374">.mw-parser-output .hlist dl,.mw-parser-output .hlist ol,.mw-parser-output .hlist ul{margin:0;padding:0}.mw-parser-output .hlist dd,.mw-parser-output .hlist dt,.mw-parser-output .hlist li{margin:0;display:inline}.mw-parser-output .hlist.inline,.mw-parser-output .hlist.inline dl,.mw-parser-output .hlist.inline ol,.mw-parser-output .hlist.inline ul,.mw-parser-output .hlist dl dl,.mw-parser-output .hlist dl ol,.mw-parser-output .hlist dl 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href="/wiki/Interferon_alpha" class="mw-redirect" title="Interferon alpha">IFN-α</a></li> <li><a href="/wiki/Interferon_beta" class="mw-redirect" title="Interferon beta">IFN-β</a></li> <li><a href="/wiki/Interferon_gamma" title="Interferon gamma">IFN-γ</a></li> <li><a href="/wiki/CXCL10" title="CXCL10">CXCL10</a></li> <li><a href="/wiki/Interleukin_4" title="Interleukin 4">IL-4</a></li> <li><a href="/wiki/Interleukin_12" title="Interleukin 12">IL-12</a></li> <li><a href="/wiki/Interleukin_18" title="Interleukin 18">IL-18</a></li> <li><a href="/wiki/Maspin" title="Maspin">maspin</a></li> <li><a href="/wiki/Meth-1" class="mw-redirect" title="Meth-1">Meth-1</a></li> <li><a href="/wiki/Meth-2" class="mw-redirect" title="Meth-2">Meth-2</a></li> <li><a href="/wiki/Osteopontin" title="Osteopontin">osteopontin</a></li> <li><a href="/wiki/Platelet_factor-4" class="mw-redirect" title="Platelet factor-4">platelet factor-4</a></li> <li><a href="/wiki/Prolactin" title="Prolactin">prolactin</a></li> <li><a href="/w/index.php?title=Proliferin-related_protein&action=edit&redlink=1" class="new" title="Proliferin-related protein (page does not exist)">proliferin-related protein</a></li> <li><a href="/wiki/Prothrombin" class="mw-redirect" title="Prothrombin">prothrombin</a> (<a href="/wiki/Kringle_domain" title="Kringle domain">kringle domain</a>-2)</li> <li><a href="/wiki/Antithrombin_III" class="mw-redirect" title="Antithrombin III">antithrombin III</a> fragment</li> <li><a href="/wiki/Osteonectin" title="Osteonectin">SPARC</a></li> <li><a href="/wiki/Thrombospondin_1" title="Thrombospondin 1">Thrombospondin 1</a></li> <li><a href="/wiki/Tissue_inhibitor_of_metalloproteinases" class="mw-redirect" title="Tissue inhibitor of metalloproteinases">TIMP</a></li> <li><a href="/wiki/Vasostatin" class="mw-redirect" title="Vasostatin">vasostatin</a></li> <li><a href="/wiki/VEGI" class="mw-redirect" title="VEGI">VEGI</a></li> <li><a href="/wiki/VEGFR-1" class="mw-redirect" title="VEGFR-1">soluble VEGFR-1</a></li> <li><a href="/wiki/NRP-1" class="mw-redirect" title="NRP-1">NRP-1</a></li> <li><a href="/wiki/Cartilage-derived_angiogenesis_inhibitor" title="Cartilage-derived angiogenesis inhibitor">CDAI</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Exogeny" title="Exogeny">Exogenous</a></th><td class="navbox-list-with-group navbox-list navbox-even hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/2-Methoxyestradiol" title="2-Methoxyestradiol">2-Methoxyestradiol</a></li> <li><a href="/wiki/Alpha-V_beta-3" class="mw-redirect" title="Alpha-V beta-3">α<sub>V</sub>β<sub>3</sub> inhibitors</a></li> <li><a href="/w/index.php?title=Angiostatic_steroid&action=edit&redlink=1" class="new" title="Angiostatic steroid (page does not exist)">angiostatic steroids</a></li> <li><a href="/wiki/Heparin" title="Heparin">heparin</a></li> <li><a href="/wiki/Angiostatin" title="Angiostatin">angiostatin</a></li> <li><a href="/wiki/Bevacizumab" title="Bevacizumab">bevacizumab</a></li> <li><a href="/wiki/Carboxyamidotriazole" title="Carboxyamidotriazole">carboxyamidotriazole</a></li> <li><a href="/wiki/Cartilage-Derived_Angiogenesis_Inhibitory_Factor" class="mw-redirect" title="Cartilage-Derived Angiogenesis Inhibitory Factor">Cartilage-Derived Angiogenesis Inhibitory Factor</a></li> <li><a href="/w/index.php?title=CM101&action=edit&redlink=1" class="new" title="CM101 (page does not exist)">CM101</a></li> <li><a href="/wiki/Endostatin" title="Endostatin">endostatin</a></li> <li><a href="/wiki/Interferon_alpha" class="mw-redirect" title="Interferon alpha">IFN-α</a></li> <li><a href="/wiki/Interleukin_12" title="Interleukin 12">IL-12</a></li> <li><a href="/wiki/Itraconazole" title="Itraconazole">itraconazole</a></li> <li><a href="/wiki/Linomide" title="Linomide">linomide</a></li> <li><a href="/wiki/Matrix_metalloproteinase_inhibitor" title="Matrix metalloproteinase inhibitor">matrix metalloproteinase inhibitors</a></li> <li><a href="/wiki/Platelet_factor-4" class="mw-redirect" title="Platelet factor-4">platelet factor-4</a></li> <li><a href="/wiki/Prolactin" title="Prolactin">prolactin</a></li> <li><a href="/wiki/SU5416" class="mw-redirect" title="SU5416">SU5416</a></li> <li><a href="/wiki/Suramin" title="Suramin">suramin</a></li> <li><a href="/wiki/Tasquinimod" title="Tasquinimod">tasquinimod</a></li> <li><a href="/w/index.php?title=Tecogalan&action=edit&redlink=1" class="new" title="Tecogalan (page does not exist)">tecogalan</a></li> <li><a href="/wiki/Tetrathiomolybdate" title="Tetrathiomolybdate">tetrathiomolybdate</a></li> <li><a href="/wiki/Thalidomide" title="Thalidomide">thalidomide</a></li> <li><a href="/wiki/Thrombospondin" title="Thrombospondin">thrombospondin</a></li> <li><a href="/wiki/Thrombospondin" title="Thrombospondin">thrombospondin</a></li> <li><a href="/wiki/TNP-470" title="TNP-470">TNP-470</a></li> <li><a href="/wiki/VEGFR" class="mw-redirect" title="VEGFR">VEGFR antagonists</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">See also</th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Angiogenesis" title="Angiogenesis">Angiogenesis</a></li> <li><a href="/wiki/Category:Angiogenesis_inhibitors" title="Category:Angiogenesis inhibitors">Angiogenesis inhibitors</a></li></ul> </div></td></tr></tbody></table></div>    </div><noscript><img src="https://login.wikimedia.org/wiki/Special:CentralAutoLogin/start?type=1x1" alt="" width="1" height="1" style="border: none; position: absolute;"></noscript> <div class="printfooter" data-nosnippet="">Retrieved from "<a dir="ltr" href="https://en.wikipedia.org/w/index.php?title=Angiogenesis_inhibitor&oldid=1233194193">https://en.wikipedia.org/w/index.php?title=Angiogenesis_inhibitor&oldid=1233194193</a>"</div></div> <div 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