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</div> <div class="pre-content heading-holder"> <div class="page-heading"> <h1 id="firstHeading" class="firstHeading mw-first-heading">Recurrent cancer</h1> <div class="tagline"></div> </div> <ul id="p-associated-pages" class="minerva__tab-container"> <li class="minerva__tab selected"> <a class="minerva__tab-text" href="/wiki/Recurrent_cancer" rel="" data-event-name="tabs.subject">Article</a> </li> <li class="minerva__tab "> <a class="minerva__tab-text" href="/wiki/Talk:Recurrent_cancer" rel="discussion" data-event-name="tabs.talk">Talk</a> </li> </ul> <nav class="page-actions-menu"> <ul id="p-views" class="page-actions-menu__list"> <li id="language-selector" class="page-actions-menu__list-item"> <a role="button" href="" data-mw="interface" data-event-name="menu.languages" title="Language" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet language-selector disabled"> Language </a> </li> <li 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id="bodyContent" class="content"> <div id="mw-content-text" class="mw-body-content"><script>function mfTempOpenSection(id){var block=document.getElementById("mf-section-"+id);block.className+=" open-block";block.previousSibling.className+=" open-block";}</script><div class="mw-content-ltr mw-parser-output" lang="en" dir="ltr"><section class="mf-section-0" id="mf-section-0"> <style data-mw-deduplicate="TemplateStyles:r1251242444">.mw-parser-output .ambox{border:1px solid #a2a9b1;border-left:10px solid #36c;background-color:#fbfbfb;box-sizing:border-box}.mw-parser-output .ambox+link+.ambox,.mw-parser-output .ambox+link+style+.ambox,.mw-parser-output .ambox+link+link+.ambox,.mw-parser-output .ambox+.mw-empty-elt+link+.ambox,.mw-parser-output .ambox+.mw-empty-elt+link+style+.ambox,.mw-parser-output .ambox+.mw-empty-elt+link+link+.ambox{margin-top:-1px}html body.mediawiki .mw-parser-output .ambox.mbox-small-left{margin:4px 1em 4px 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.ambox{display:none!important}}</style><table class="box-Lead_too_long plainlinks metadata ambox ambox-style ambox-lead_too_long" role="presentation"><tbody><tr><td class="mbox-text"><div class="mbox-text-span">This article's <a href="/wiki/Wikipedia:Manual_of_Style/Lead_section" title="Wikipedia:Manual of Style/Lead section">lead section</a> may be too long. Please read the <a href="/wiki/Wikipedia:Manual_of_Style/Lead_section#Length" title="Wikipedia:Manual of Style/Lead section">length guidelines</a> and help <a class="external text" href="https://en.wikipedia.org/w/index.php?title=Recurrent_cancer&action=edit">move details into the article's body</a>. (January 2023)</div></td></tr></tbody></table> Recurrent cancer is any form of <a href="/wiki/Cancer" title="Cancer">cancer</a> that has returned or recurred when a fraction of primary <a href="/wiki/Tumor_cells" class="mw-redirect" title="Tumor cells">tumor cells</a> evade the effects of <a href="/wiki/Treatment_of_cancer" class="mw-redirect" title="Treatment of cancer">treatment</a> and survive in small spaces that are undetectable by <a href="/wiki/Diagnostic_tests" class="mw-redirect" title="Diagnostic tests">diagnostic tests</a>. The initial <a href="/wiki/Tumor" class="mw-redirect" title="Tumor">tumor</a> may become the site of cancer’s return or it may spread to another part of the body.<a href="#cite_note-1">[1]</a> These surviving cells accumulate various genetic changes over time, eventually producing a new tumor cell. It can take up to weeks, months, or even years for cancer to return. Following surgery and/or <a href="/wiki/Chemotherapy" title="Chemotherapy">chemotherapy</a> or <a href="/wiki/Radiation_therapy" title="Radiation therapy">radiotherapy</a>, certain tumor cells may persist and develop resistance to treatment and eventually develop into new tumors. The rate of cancer recurrence is determined by many factors, including age, sex, cancer type, treatment duration, stage of advancement, grade of original tumor, and cancer-specific risk factors.<a href="#cite_note-2">[2]</a><a href="#cite_note-:0-3">[3]</a><a href="#cite_note-4">[4]</a> If recurrent cancer has already moved to other body parts or has developed <a href="/w/index.php?title=Chemo-resistance&action=edit&redlink=1" class="new" title="Chemo-resistance (page does not exist)">chemo-resistance</a> then it may be more aggressive than original cancer. In general, the severity of cancer increases with a shorter duration of time between initial treatment and its return.<a href="#cite_note-:0-3">[3]</a> Cancers with the highest recurrence rates include <a href="/wiki/Glioblastoma" title="Glioblastoma">Glioblastoma</a> with a recurrence rate of almost 100%,<a href="#cite_note-5">[5]</a> <a href="/wiki/Epithelial_ovarian_cancer" class="mw-redirect" title="Epithelial ovarian cancer">Epithelial ovarian cancer</a> with a recurrence rate of 85%,<a href="#cite_note-6">[6]</a> and <a href="/wiki/Bladder_cancer" title="Bladder cancer">Bladder cancer</a> with a recurrence rate of 30-54%<a href="#cite_note-7">[7]</a> <div id="toc" class="toc" role="navigation" aria-labelledby="mw-toc-heading"><input type="checkbox" role="button" id="toctogglecheckbox" class="toctogglecheckbox" style="display:none"><div class="toctitle" lang="en" dir="ltr"><h2 id="mw-toc-heading">Contents</h2><label class="toctogglelabel" for="toctogglecheckbox"></label></div> <ul> <li class="toclevel-1 tocsection-1"><a href="#Types">1 Types</a></li> <li class="toclevel-1 tocsection-2"><a href="#Causes">2 Causes</a> <ul> <li class="toclevel-2 tocsection-3"><a href="#Cancer_stem_cells">2.1 Cancer stem cells</a></li> <li class="toclevel-2 tocsection-4"><a href="#Neosis">2.2 Neosis</a></li> <li class="toclevel-2 tocsection-5"><a href="#Phoenix_rising">2.3 Phoenix rising</a></li> <li class="toclevel-2 tocsection-6"><a href="#Cell_stress_and_dormancy">2.4 Cell stress and dormancy</a></li> </ul> </li> <li class="toclevel-1 tocsection-7"><a href="#Diagnosis">3 Diagnosis</a></li> <li class="toclevel-1 tocsection-8"><a href="#Treatment">4 Treatment</a></li> <li class="toclevel-1 tocsection-9"><a href="#References">5 References</a></li> </ul> </div> </section><div class="mw-heading mw-heading2 section-heading" onclick="mfTempOpenSection(1)"><h2 id="Types">Types</h2> <a role="button" href="/w/index.php?title=Recurrent_cancer&action=edit&section=1" title="Edit section: Types" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> edit </a> </div><section class="mf-section-1 collapsible-block" id="mf-section-1"> There are three types of recurrent cancers: <ul><li>Local recurrence - Cancer returns to the same original site.<a href="#cite_note-8">[8]</a><a href="#cite_note-9">[9]</a></li> <li>Regional recurrence - Cancer is detected in tissue or lymph nodes near the original site.<a href="#cite_note-10">[10]</a></li> <li>Distant recurrence - Cancer has been detected in tissue far from the original site. Also known as metastatic recurrence.<a href="#cite_note-11">[11]</a><a href="#cite_note-12">[12]</a></li></ul> </section><div class="mw-heading mw-heading2 section-heading" onclick="mfTempOpenSection(2)"><h2 id="Causes">Causes</h2> <a role="button" href="/w/index.php?title=Recurrent_cancer&action=edit&section=2" title="Edit section: Causes" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> edit </a> </div><section class="mf-section-2 collapsible-block" id="mf-section-2"> <div class="mw-heading mw-heading3"><h3 id="Cancer_stem_cells">Cancer stem cells</h3> <a role="button" href="/w/index.php?title=Recurrent_cancer&action=edit&section=3" title="Edit section: Cancer stem cells" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> edit </a> </div> <a href="/wiki/Cancer_stem_cell" title="Cancer stem cell">Cancer stem cells</a> (CSC) are a small population of the entire tumor cell mass, that are responsible for early formation, progression, and recurrence of cancer. It also contributes to <a href="/wiki/Drug_resistance" title="Drug resistance">drug resistance</a>.<a href="#cite_note-13">[13]</a><a href="#cite_note-14">[14]</a> CSCs are thought to originate from normal <a href="/wiki/Stem_cell" title="Stem cell">stem cells</a>, progenitor cells or <a href="/wiki/Differentiated_cell" class="mw-redirect" title="Differentiated cell">differentiated cells</a> as a result of cumulative genetic <a href="/wiki/Mutation" title="Mutation">mutation</a> and subsequent <a href="/wiki/Genome_instability" title="Genome instability">genomic instability</a>.<a href="#cite_note-15">[15]</a> They are found in the <a href="/wiki/Tumor_microenvironment_of_metastasis" class="mw-redirect" title="Tumor microenvironment of metastasis">tumor microenvironment's</a> specialized niches. CSCs have so far been found in a variety of tumors, including those of the <a href="/wiki/Brain_tumor" title="Brain tumor">brain</a>, <a href="/wiki/Breast_cancer" title="Breast cancer">breast</a>, <a href="/wiki/Ovarian_cancer" title="Ovarian cancer">ovary</a>, <a href="/wiki/Head_and_neck_cancer" title="Head and neck cancer">head and neck</a>, etc.<a href="#cite_note-16">[16]</a><a href="#cite_note-17">[17]</a><a href="#cite_note-18">[18]</a><a href="#cite_note-19">[19]</a><a href="#cite_note-20">[20]</a> CSCs have the ability of self-proliferation just like regular stem cells. A single CSC can divide asymmetrically into one CSC and one differentiated tumor cell. The tumor is majority made up of the latter cells.<a href="#cite_note-21">[21]</a> In some cancers CSCs are quiescent for long period of time, making them ineffective to the treatment. Therefore, even decades after the primary cancer has been fully treated, the reactivation of the inactive CSCs may lead to tumor recurrence.<a href="#cite_note-22">[22]</a><a href="#cite_note-23">[23]</a> <div class="mw-heading mw-heading3"><h3 id="Neosis">Neosis</h3> <a role="button" href="/w/index.php?title=Recurrent_cancer&action=edit&section=4" title="Edit section: Neosis" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> edit </a> </div> <a href="/wiki/Hypoxia_(medical)" class="mw-redirect" title="Hypoxia (medical)">Hypoxia</a>, <a href="/wiki/Chemotherapeutic_agents" class="mw-redirect" title="Chemotherapeutic agents">chemotherapeutic agents</a>, and <a href="/wiki/Radiation_therapy" title="Radiation therapy">radiation</a> can generate <a href="/w/index.php?title=Polyploid_Giant_Cancer_Cells&action=edit&redlink=1" class="new" title="Polyploid Giant Cancer Cells (page does not exist)">Polyploid Giant Cancer Cells</a> (PGCC). Some PGCCs have the ability to undergo neosis, which is characterized by nuclear budding <a href="/wiki/Karyokinesis" class="mw-redirect" title="Karyokinesis">karyokinesis</a>, asymmetric intracellular cytokinesis and the generation of <a href="/w/index.php?title=Raju_cells&action=edit&redlink=1" class="new" title="Raju cells (page does not exist)">Raju cells</a>, which are tiny mononuclear cells having stem cell like characteristics. These cells play a role in cancer recurrence and therapy resistance.<a href="#cite_note-24">[24]</a> <div class="mw-heading mw-heading3"><h3 id="Phoenix_rising">Phoenix rising</h3> <a role="button" href="/w/index.php?title=Recurrent_cancer&action=edit&section=5" title="Edit section: Phoenix rising" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> edit </a> </div> Phoenix rising is a process by which dead cells send signals that promote growth and division, generating new cells.<a href="#cite_note-25">[25]</a> After a tissue injury, stem cells present in and around the injured tissue play a crucial role in replenishing the damaged ones. It is theorized that molecules released from wounded cells trigger stem cells' migration to that site, followed by differentiation and proliferation.<a href="#cite_note-26">[26]</a> Through the process of <a href="/wiki/Apoptosis" title="Apoptosis">apoptosis</a>, the dying tumor cells provide growth signals and repair radiation-damaged tumors. PGE2 is released by apoptotic cells in a caspase-dependent manner, which aids cancer stem cells and cancer progenitor cells in expanding and multiplying.<a href="#cite_note-27">[27]</a> <div class="mw-heading mw-heading3"><h3 id="Cell_stress_and_dormancy">Cell stress and dormancy</h3> <a role="button" href="/w/index.php?title=Recurrent_cancer&action=edit&section=6" title="Edit section: Cell stress and dormancy" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> edit </a> </div> Cancer recurrence (relapse) is ascribed to malignant cells that evade therapy: small numbers of cancer cells may remain undetected, and dormant, pausing their proliferation for long time. This can occur also by mechanisms different from cell cycle quiescence.<a href="#cite_note-28">[28]</a><a href="#cite_note-29">[29]</a> In fact, the effects of therapy that kills most cancer cells, may cause a few of them to pause proliferation instead of dying.<a href="#cite_note-30">[30]</a> While the precise mechanism of growth arrest is not entirely clear and may not be uniform across cancer cases, malignant cells that survive chemotherapy make several metabolic adaptations and possess altered configuration of key positions of their chromatin, the material that packages their DNA. This has as result that certain conditions can trigger expression of genes that reignite cancer cell growth, causing proliferation, and additionally these conditions may trigger aberrant expression of genes that cause changes in the host tissue, which also permit cancer growth.<a href="#cite_note-31">[31]</a> </section><div class="mw-heading mw-heading2 section-heading" onclick="mfTempOpenSection(3)"><h2 id="Diagnosis">Diagnosis</h2> <a role="button" href="/w/index.php?title=Recurrent_cancer&action=edit&section=7" title="Edit section: Diagnosis" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> edit </a> </div><section class="mf-section-3 collapsible-block" id="mf-section-3"> Early diagnosis of recurrence is important and can improve the prognosis and survival of patients with cancer.<a href="#cite_note-32">[32]</a> Depending on the primary cancer type, several laboratory and imaging tests, as well as numerous invasive procedures, are used for the diagnosis of recurring cancers.<a href="#cite_note-33">[33]</a><a href="#cite_note-34">[34]</a> <a href="/wiki/Malignant_tumors" class="mw-redirect" title="Malignant tumors">Malignant tumors</a> develop and secrete biologic chemicals known as <a href="/wiki/Tumor_marker" title="Tumor marker">tumor markers</a> that are detectable in the bloodstream. These markers might ideally be used to screen for cancer, diagnose it, and track how effectively it responds to treatment.<a href="#cite_note-35">[35]</a> </section><div class="mw-heading mw-heading2 section-heading" onclick="mfTempOpenSection(4)"><h2 id="Treatment">Treatment</h2> <a role="button" href="/w/index.php?title=Recurrent_cancer&action=edit&section=8" title="Edit section: Treatment" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> edit </a> </div><section class="mf-section-4 collapsible-block" id="mf-section-4"> The inherent limits of current cancer therapy approaches usually result in treatment failure. <a href="/wiki/Chemotherapy" title="Chemotherapy">Chemotherapy</a> and <a href="/wiki/Radiation_therapy" title="Radiation therapy">radiation therapy</a> resistance is a common factor in the failure of treatment for many cancers.<a href="#cite_note-36">[36]</a> Additionally, because most treatments cannot completely eradicate CSCs, many methods that are not adequately selective against CSCs might be harmful to healthy tissues, and patients frequently run the risk of recurrence and <a href="/wiki/Metastasis" title="Metastasis">metastasis</a>.<a href="#cite_note-37">[37]</a> Recent years have seen the development of numerous treatments with the goal of eliminating CSC. Targeting CSC surface markers, the ABC cascade, the <a href="/wiki/Tumor_microenvironment" title="Tumor microenvironment">microenvironment</a>, or <a href="/wiki/Signal_cascade" class="mw-redirect" title="Signal cascade">signal cascades</a> could all help kill CSCs. There are numerous drugs targeting these markers or pathways, which are being tested in clinical trials. The treatment varies from cancer to cancer and patient to patient.<a href="#cite_note-38">[38]</a><a href="#cite_note-39">[39]</a><a href="#cite_note-40">[40]</a><a href="#cite_note-41">[41]</a> </section><div class="mw-heading mw-heading2 section-heading" onclick="mfTempOpenSection(5)"><h2 id="References">References</h2> <a role="button" href="/w/index.php?title=Recurrent_cancer&action=edit&section=9" title="Edit section: References" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> edit </a> </div><section class="mf-section-5 collapsible-block" id="mf-section-5"> <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"><a href="#cite_ref-1">^</a> <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 class="citation web cs1"><a rel="nofollow" class="external text" href="https://www.cancer.gov/publications/dictionaries/cancer-terms/def/recurrent-cancer">"https://www.cancer.gov/publications/dictionaries/cancer-terms/def/recurrent-cancer"</a>. www.cancer.gov. 2011-02-02. 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