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(PDF) Cancer stem cell (a)symmetry & plasticity: Tumorigenesis and therapy relevance
<!DOCTYPE html> <html > <head> <meta charset="utf-8"> <meta rel="search" type="application/opensearchdescription+xml" href="/open_search.xml" title="Academia.edu"> <meta content="width=device-width, initial-scale=1" name="viewport"> <meta name="google-site-verification" content="bKJMBZA7E43xhDOopFZkssMMkBRjvYERV-NaN4R6mrs"> <meta name="csrf-param" content="authenticity_token" /> <meta name="csrf-token" content="My13VW3f4BymBs57oB2hR7mK9pwW5T_2_J86c8MK0r2guybwr5s-JpiWwV3SxiI78A7a-cs6MCGaMGCBKny0HA" /> <meta name="citation_title" content="Cancer stem cell (a)symmetry &amp; plasticity: Tumorigenesis and therapy relevance" /> <meta name="citation_author" content="Masoud Najafi" /> <meta name="twitter:card" content="summary" /> <meta name="twitter:url" content="https://www.academia.edu/42225106/Cancer_stem_cell_a_symmetry_and_plasticity_Tumorigenesis_and_therapy_relevance" /> <meta name="twitter:title" content="Cancer stem cell (a)symmetry & plasticity: Tumorigenesis and therapy relevance" /> <meta name="twitter:description" content="Cancer stem cells (CSCs) are self-renewal population localized within cancer niches and play critical roles in tumor initiation, recurrence and metastasis. Despite extensive research, challenges about identity of CSCs and combating them in cancer" /> <meta name="twitter:image" content="http://a.academia-assets.com/images/twitter-card.jpeg" /> <meta property="fb:app_id" content="2369844204" /> <meta property="og:type" content="article" /> <meta property="og:url" content="https://www.academia.edu/42225106/Cancer_stem_cell_a_symmetry_and_plasticity_Tumorigenesis_and_therapy_relevance" /> <meta property="og:title" content="Cancer stem cell (a)symmetry & plasticity: Tumorigenesis and therapy relevance" /> <meta property="og:image" content="http://a.academia-assets.com/images/open-graph-icons/fb-paper.gif" /> <meta property="og:description" content="Cancer stem cells (CSCs) are self-renewal population localized within cancer niches and play critical roles in tumor initiation, recurrence and metastasis. Despite extensive research, challenges about identity of CSCs and combating them in cancer" /> <meta property="article:author" content="https://kums.academia.edu/MasoudNajafi" /> <meta name="description" content="Cancer stem cells (CSCs) are self-renewal population localized within cancer niches and play critical roles in tumor initiation, recurrence and metastasis. Despite extensive research, challenges about identity of CSCs and combating them in cancer" /> <title>(PDF) Cancer stem cell (a)symmetry & plasticity: Tumorigenesis and therapy relevance</title> <link rel="canonical" href="https://www.academia.edu/41114209/Cancer_stem_cell_a_symmetry_and_plasticity_Tumorigenesis_and_therapy_relevance" /> <script async src="https://www.googletagmanager.com/gtag/js?id=G-5VKX33P2DS"></script> <script> window.dataLayer = window.dataLayer || []; function gtag(){dataLayer.push(arguments);} gtag('js', new Date()); gtag('config', 'G-5VKX33P2DS', { cookie_domain: 'academia.edu', send_page_view: false, }); gtag('event', 'page_view', { 'controller': "single_work", 'action': "show", 'controller_action': 'single_work#show', 'logged_in': 'false', 'edge': 'unknown', // Send nil if there is no A/B test bucket, in case some records get logged // with missing data - that way we can distinguish between the two cases. // ab_test_bucket should be of the form <ab_test_name>:<bucket> 'ab_test_bucket': null, }) </script> <script> var $controller_name = 'single_work'; var $action_name = "show"; var $rails_env = 'production'; var $app_rev = '29cbb9485f79f49ca3eb38b6f0905739256f19a4'; var $domain = 'academia.edu'; var $app_host = "academia.edu"; var $asset_host = "academia-assets.com"; var $start_time = new Date().getTime(); var $recaptcha_key = "6LdxlRMTAAAAADnu_zyLhLg0YF9uACwz78shpjJB"; var $recaptcha_invisible_key = "6Lf3KHUUAAAAACggoMpmGJdQDtiyrjVlvGJ6BbAj"; var $disableClientRecordHit = false; </script> <script> window.require = { config: function() { return function() {} } } </script> <script> window.Aedu = window.Aedu || {}; window.Aedu.hit_data = null; window.Aedu.serverRenderTime = new Date(1740347634000); window.Aedu.timeDifference = new Date().getTime() - 1740347634000; </script> <script type="application/ld+json">{"@context":"https://schema.org","@type":"ScholarlyArticle","abstract":"Cancer stem cells (CSCs) are self-renewal population localized within cancer niches and play critical roles in tumor initiation, recurrence and metastasis. Despite extensive research, challenges about identity of CSCs and combating them in cancer therapy still remain steady. Cellular plasticity is a cardinal feature of tumor micro-environment (TME) tremendously influencing tumor aggressive behavior. Plasticity and CSC a (symmetry) are interconnecting processes essential for shaping a cancer through nurturing a wide number of cells with tumor promoting capacities. The plastic nature of TME cellularity infers that destemming just CSCs is not sufficient in respect with therapy, especially for high-grade cancers-instead, deploying mechanisms to retard tumor type-dependent TME-CSC interplay is a suggested strategy for making a durable remission of cancer. This requires extending our understanding about CSC divisional profiling and plasticity in order to find critical drivers in cancer progression.","author":[{"@context":"https://schema.org","@type":"Person","name":"Masoud Najafi","url":"https://kums.academia.edu/MasoudNajafi"}],"contributor":[],"dateCreated":"2020-03-15","headline":"Cancer stem cell (a)symmetry \u0026 plasticity: Tumorigenesis and therapy relevance","image":"https://attachments.academia-assets.com/62374440/thumbnails/1.jpg","inLanguage":"en","keywords":[],"publisher":{"@context":"https://schema.org","@type":"Organization","name":null},"sourceOrganization":[{"@context":"https://schema.org","@type":"EducationalOrganization","name":"kums"}],"thumbnailUrl":"https://attachments.academia-assets.com/62374440/thumbnails/1.jpg","url":"https://www.academia.edu/42225106/Cancer_stem_cell_a_symmetry_and_plasticity_Tumorigenesis_and_therapy_relevance"}</script><style type="text/css">@media(max-width: 567px){:root{--token-mode: 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window.loswp.work = {"work":{"id":42225106,"created_at":"2020-03-15T13:42:10.059-07:00","from_world_paper_id":null,"updated_at":"2024-11-28T04:57:09.533-08:00","_data":{"abstract":"Cancer stem cells (CSCs) are self-renewal population localized within cancer niches and play critical roles in tumor initiation, recurrence and metastasis. Despite extensive research, challenges about identity of CSCs and combating them in cancer therapy still remain steady. Cellular plasticity is a cardinal feature of tumor micro-environment (TME) tremendously influencing tumor aggressive behavior. Plasticity and CSC a (symmetry) are interconnecting processes essential for shaping a cancer through nurturing a wide number of cells with tumor promoting capacities. The plastic nature of TME cellularity infers that destemming just CSCs is not sufficient in respect with therapy, especially for high-grade cancers-instead, deploying mechanisms to retard tumor type-dependent TME-CSC interplay is a suggested strategy for making a durable remission of cancer. This requires extending our understanding about CSC divisional profiling and plasticity in order to find critical drivers in cancer progression.","ai_title_tag":"Cancer Stem Cell Plasticity and Its Impact on Tumorigenesis"},"document_type":"paper","pre_hit_view_count_baseline":null,"quality":"high","language":"en","title":"Cancer stem cell (a)symmetry \u0026 plasticity: Tumorigenesis and therapy relevance","broadcastable":true,"draft":null,"has_indexable_attachment":true,"indexable":true}}["work"]; window.loswp.workCoauthors = [652424]; window.loswp.locale = "en"; window.loswp.countryCode = "SG"; window.loswp.cwvAbTestBucket = ""; window.loswp.designVariant = "ds_vanilla"; window.loswp.fullPageMobileSutdModalVariant = "control"; window.loswp.useOptimizedScribd4genScript = false; window.loginModal = {}; window.loginModal.appleClientId = 'edu.academia.applesignon'; window.userInChina = "false";</script><script defer="" src="https://accounts.google.com/gsi/client"></script><div class="ds-loswp-container"><div class="ds-work-card--grid-container"><div class="ds-work-card--container js-loswp-work-card"><div class="ds-work-card--cover"><div class="ds-work-cover--wrapper"><div class="ds-work-cover--container"><button class="ds-work-cover--clickable js-swp-download-button" data-signup-modal="{"location":"swp-splash-paper-cover","attachmentId":62374440,"attachmentType":"pdf"}"><img alt="First page of “Cancer stem cell (a)symmetry & plasticity: Tumorigenesis and therapy relevance”" class="ds-work-cover--cover-thumbnail" src="https://0.academia-photos.com/attachment_thumbnails/62374440/mini_magick20200316-338-1ilybwr.png?1584404069" /><img alt="PDF Icon" class="ds-work-cover--file-icon" src="//a.academia-assets.com/images/single_work_splash/adobe_icon.svg" /><div class="ds-work-cover--hover-container"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span><p>Download Free PDF</p></div><div class="ds-work-cover--ribbon-container">Download Free PDF</div><div class="ds-work-cover--ribbon-triangle"></div></button></div></div></div><div class="ds-work-card--work-information"><h1 class="ds-work-card--work-title">Cancer stem cell (a)symmetry & plasticity: Tumorigenesis and therapy relevance</h1><div class="ds-work-card--work-authors ds-work-card--detail"><a class="ds-work-card--author js-wsj-grid-card-author ds2-5-body-md ds2-5-body-link" data-author-id="652424" href="https://kums.academia.edu/MasoudNajafi"><img alt="Profile image of Masoud Najafi" class="ds-work-card--author-avatar" src="//a.academia-assets.com/images/s65_no_pic.png" />Masoud Najafi</a></div><div class="ds-work-card--detail"><div class="ds-work-card--work-metadata"><div class="ds-work-card--work-metadata__stat"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">visibility</span><p class="ds2-5-body-sm" id="work-metadata-view-count">…</p></div><div class="ds-work-card--work-metadata__stat"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">description</span><p class="ds2-5-body-sm">6 pages</p></div><div class="ds-work-card--work-metadata__stat"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">link</span><p class="ds2-5-body-sm">1 file</p></div></div><script>(async () => { const workId = 42225106; 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if (!viewCountBody) { throw new Error('Failed to find work views element'); } viewCountBody.textContent = `${commaizedViewCount} views`; } catch (error) { // Remove the whole views element if there was some issue parsing. document.getElementById('work-metadata-view-count')?.parentNode?.remove(); throw new Error(`Failed to parse view count: ${viewCount}`, error); } }; // If the DOM is still loading, wait for it to be ready before updating the view count. if (document.readyState === "loading") { document.addEventListener('DOMContentLoaded', () => { updateViewCount(viewCount); }); // Otherwise, just update it immediately. } else { updateViewCount(viewCount); } })();</script></div><p class="ds-work-card--work-abstract ds-work-card--detail ds2-5-body-md">Cancer stem cells (CSCs) are self-renewal population localized within cancer niches and play critical roles in tumor initiation, recurrence and metastasis. Despite extensive research, challenges about identity of CSCs and combating them in cancer therapy still remain steady. Cellular plasticity is a cardinal feature of tumor micro-environment (TME) tremendously influencing tumor aggressive behavior. Plasticity and CSC a (symmetry) are interconnecting processes essential for shaping a cancer through nurturing a wide number of cells with tumor promoting capacities. The plastic nature of TME cellularity infers that destemming just CSCs is not sufficient in respect with therapy, especially for high-grade cancers-instead, deploying mechanisms to retard tumor type-dependent TME-CSC interplay is a suggested strategy for making a durable remission of cancer. This requires extending our understanding about CSC divisional profiling and plasticity in order to find critical drivers in cancer progression.</p><div class="ds-work-card--button-container"><button class="ds2-5-button js-swp-download-button" data-signup-modal="{"location":"continue-reading-button--work-card","attachmentId":62374440,"attachmentType":"pdf","workUrl":"https://www.academia.edu/42225106/Cancer_stem_cell_a_symmetry_and_plasticity_Tumorigenesis_and_therapy_relevance"}">See full PDF</button><button class="ds2-5-button ds2-5-button--secondary js-swp-download-button" data-signup-modal="{"location":"download-pdf-button--work-card","attachmentId":62374440,"attachmentType":"pdf","workUrl":"https://www.academia.edu/42225106/Cancer_stem_cell_a_symmetry_and_plasticity_Tumorigenesis_and_therapy_relevance"}"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span>Download PDF</button></div><div class="ds-signup-banner-trigger-container"><div class="ds-signup-banner-trigger ds-signup-banner-trigger-control"></div></div><div class="ds-signup-banner ds-signup-banner-control"><div id="ds-signup-banner-close-button"><button class="ds2-5-button ds2-5-button--secondary ds2-5-button--inverse"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">close</span></button></div><div class="ds-signup-banner-ctas"><img src="//a.academia-assets.com/images/academia-logo-capital-white.svg" /><h4 class="ds2-5-heading-serif-sm">Sign up for access to the world's latest research</h4><button class="ds2-5-button ds2-5-button--inverse ds2-5-button--full-width js-swp-download-button" data-signup-modal="{"location":"signup-banner"}">Sign up for free<span class="material-symbols-outlined" style="font-size: 20px" translate="no">arrow_forward</span></button></div><div class="ds-signup-banner-divider"></div><div class="ds-signup-banner-reasons"><div class="ds-signup-banner-reasons-item"><span class="material-symbols-outlined" style="font-size: 24px" translate="no">check</span><span>Get notified about relevant papers</span></div><div class="ds-signup-banner-reasons-item"><span class="material-symbols-outlined" style="font-size: 24px" translate="no">check</span><span>Save papers to use in your research</span></div><div class="ds-signup-banner-reasons-item"><span class="material-symbols-outlined" style="font-size: 24px" translate="no">check</span><span>Join the discussion with peers</span></div><div class="ds-signup-banner-reasons-item"><span class="material-symbols-outlined" style="font-size: 24px" translate="no">check</span><span>Track your impact</span></div></div></div><script>(() => { // Set up signup banner show/hide behavior: // 1. 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However, despite their importance, the molecular pathways involved in generating invasive, metastatic, and therapy-resistant CSCs remain poorly understood. The enrichment of cells with a mesenchymal/CSC phenotype following therapy has been interpreted in two different ways. The original interpretation posited that therapy kills non-CSCs while sparing pre-existing CSCs. However, evidence is emerging that suggests non-CSCs can be induced into a transient, drug-tolerant, CSC-like state by chemotherapy. The ability to transition between distinct cell states may be as critical for the survival of tumor cells following therapy as it is for metastatic progression. Therefore, inhibition of the pathways that promote E-M and CSC plasticity may suppress tumor recurrence following chemotherapy. He...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Cancer Stem Cell Plasticity Drives Therapeutic Resistance","attachmentId":77338504,"attachmentType":"pdf","work_url":"https://www.academia.edu/65966772/Cancer_Stem_Cell_Plasticity_Drives_Therapeutic_Resistance","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/65966772/Cancer_Stem_Cell_Plasticity_Drives_Therapeutic_Resistance"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="1" data-entity-id="98143119" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/98143119/Dissecting_Tumor_Growth_The_Role_of_Cancer_Stem_Cells_in_Drug_Resistance_and_Recurrence">Dissecting Tumor Growth: The Role of Cancer Stem Cells in Drug Resistance and Recurrence</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="260641861" href="https://penghuoth.academia.edu/KhawajaHusnainHaider">Khawaja Husnain Haider</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Cancers, 2022</p><p class="ds-related-work--abstract ds2-5-body-sm">Emerging evidence suggests that a small subpopulation of cancer stem cells (CSCs) is responsible for initiation, progression, and metastasis cascade in tumors. CSCs share characteristics with normal stem cells, i.e., self-renewal and differentiation potential, suggesting that they can drive cancer progression. Consequently, targeting CSCs to prevent tumor growth or regrowth might offer a chance to lead the fight against cancer. CSCs create their niche, a specific area within tissue with a unique microenvironment that sustains their vital functions. Interactions between CSCs and their niches play a critical role in regulating CSCs’ self-renewal and tumorigenesis. Differences observed in the frequency of CSCs, due to the phenotypic plasticity of many cancer cells, remain a challenge in cancer therapeutics, since CSCs can modulate their transcriptional activities into a more stem-like state to protect themselves from destruction. This plasticity represents an essential step for future ...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Dissecting Tumor Growth: The Role of Cancer Stem Cells in Drug Resistance and Recurrence","attachmentId":99575328,"attachmentType":"pdf","work_url":"https://www.academia.edu/98143119/Dissecting_Tumor_Growth_The_Role_of_Cancer_Stem_Cells_in_Drug_Resistance_and_Recurrence","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/98143119/Dissecting_Tumor_Growth_The_Role_of_Cancer_Stem_Cells_in_Drug_Resistance_and_Recurrence"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="2" data-entity-id="118602672" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/118602672/Cancer_Stem_Cell_Plasticity_A_Deadly_Deal">Cancer Stem Cell Plasticity A Deadly Deal</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="132609831" href="https://independent.academia.edu/ReshmaMurali7">Reshma Murali</a></div><p class="ds-related-work--metadata ds2-5-body-xs">2019</p><p class="ds-related-work--abstract ds2-5-body-sm">Intratumoral heterogeneity is a major ongoing challenge in the effective therapeutic targeting of cancer. Accumulating evidence suggests that a fraction of cells within a tumor termed Cancer Stem Cells (CSCs) are primarily responsible for this diversity resulting in therapeutic resistance and metastasis. Adding to this complexity, recent studies have shown that there can be different subpopulations of CSCs with varying biochemical and biophysical traits resulting in varied dissemination and drug-resistance potential. Moreover, cancer cells can exhibit a high level of plasticity or the ability to dynamically switch between CSC and non-CSC states or among different subsets of CSCs. The molecular mechanisms underlying such plasticity has been under extensive investigation and the trans-differentiation process of Epithelial to Mesenchymal transition (EMT) has been identified as a major contributing factor. Besides genetic and epigenetic factors, CSC plasticity is also shaped by non-cell...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Cancer Stem Cell Plasticity A Deadly Deal","attachmentId":114189253,"attachmentType":"pdf","work_url":"https://www.academia.edu/118602672/Cancer_Stem_Cell_Plasticity_A_Deadly_Deal","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/118602672/Cancer_Stem_Cell_Plasticity_A_Deadly_Deal"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="3" data-entity-id="121059964" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/121059964/Understanding_cancer_stem_cell_heterogeneity_and_plasticity">Understanding cancer stem cell heterogeneity and plasticity</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="206832800" href="https://independent.academia.edu/DeanTang2">Dean Tang</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Cell Research, 2012</p><p class="ds-related-work--abstract ds2-5-body-sm">Heterogeneity is an omnipresent feature of mammalian cells in vitro and in vivo. It has been recently realized that even mouse and human embryonic stem cells under the best culture conditions are heterogeneous containing pluripotent as well as partially committed cells. Somatic stem cells in adult organs are also heterogeneous, containing many subpopulations of self-renewing cells with distinct regenerative capacity. The differentiated progeny of adult stem cells also retain significant developmental plasticity that can be induced by a wide variety of experimental approaches. Like normal stem cells, recent data suggest that cancer stem cells (CSCs) similarly display significant phenotypic and functional heterogeneity, and that the CSC progeny can manifest diverse plasticity. Here, I discuss CSC heterogeneity and plasticity in the context of tumor development and progression, and by comparing with normal stem cell development. Appreciation of cancer cell plasticity entails a revision to the earlier concept that only the tumorigenic subset in the tumor needs to be targeted. By understanding the interrelationship between CSCs and their differentiated progeny, we can hope to develop better therapeutic regimens that can prevent the emergence of tumor cell variants that are able to found a new tumor and distant metastases.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Understanding cancer stem cell heterogeneity and plasticity","attachmentId":116037523,"attachmentType":"pdf","work_url":"https://www.academia.edu/121059964/Understanding_cancer_stem_cell_heterogeneity_and_plasticity","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/121059964/Understanding_cancer_stem_cell_heterogeneity_and_plasticity"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="4" data-entity-id="52953044" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/52953044/Impact_of_the_Tumor_Microenvironment_on_Tumor_Heterogeneity_and_Consequences_for_Cancer_Cell_Plasticity_and_Stemness">Impact of the Tumor Microenvironment on Tumor Heterogeneity and Consequences for Cancer Cell Plasticity and Stemness</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="50196153" href="https://independent.academia.edu/RalfHass">Ralf Hass</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Cancers</p><p class="ds-related-work--abstract ds2-5-body-sm">Tumor heterogeneity is considered the major cause of treatment failure in current cancer therapies. This feature of solid tumors is not only the result of clonal outgrowth of cells with genetic mutations, but also of epigenetic alterations induced by physical and chemical signals from the tumor microenvironment (TME). Besides fibroblasts, endothelial and immune cells, mesenchymal stroma/stem-like cells (MSCs) and tumor-associated macrophages (TAMs) intimately crosstalk with cancer cells and can exhibit both anti- and pro-tumorigenic effects. MSCs can alter cancer cellular phenotypes to increase cancer cell plasticity, eventually resulting in the generation of cancer stem cells (CSCs). The shift between different phenotypic states (phenotype switching) of CSCs is controlled via both genetic programs, such as epithelial-mesenchymal transdifferentiation or retrodifferentiation, and epigenetic alterations triggered by signals from the TME, like hypoxia, spatial heterogeneity or stromal ...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Impact of the Tumor Microenvironment on Tumor Heterogeneity and Consequences for Cancer Cell Plasticity and Stemness","attachmentId":69966296,"attachmentType":"pdf","work_url":"https://www.academia.edu/52953044/Impact_of_the_Tumor_Microenvironment_on_Tumor_Heterogeneity_and_Consequences_for_Cancer_Cell_Plasticity_and_Stemness","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/52953044/Impact_of_the_Tumor_Microenvironment_on_Tumor_Heterogeneity_and_Consequences_for_Cancer_Cell_Plasticity_and_Stemness"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="5" data-entity-id="118602597" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/118602597/The_role_of_cancer_stem_cells_in_tumor_heterogeneity_and_resistance_to_therapy">The role of cancer stem cells in tumor heterogeneity and resistance to therapy</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="132609831" href="https://independent.academia.edu/ReshmaMurali7">Reshma Murali</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Canadian Journal of Physiology and Pharmacology, 2017</p><p class="ds-related-work--abstract ds2-5-body-sm">Cancer is a heterogenous disease displaying marked inter- and intra-tumoral diversity. The existence of cancer stem cells (CSCs) has been experimentally demonstrated in a number of cancer types as a subpopulation of tumor cells that drives the tumorigenic and metastatic properties of the entire cancer. Thus, eradication of the CSC population is critical for the complete ablation of a tumor. This is, however, confounded by the inherent resistance of CSCs to standard anticancer therapies, eventually leading to the outgrowth of resistant tumor cells and relapse in patients. The cellular mechanisms of therapy resistance in CSCs are ascribed to several factors including a state of quiescence, an enhanced DNA damage response and active repair mechanisms, up-regulated expression of drug efflux transporters, as well as the activation of pro-survival signaling pathways and inactivation of apoptotic signaling. Understanding the mechanisms underlying the acquisition of resistance to therapy ma...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"The role of cancer stem cells in tumor heterogeneity and resistance to therapy","attachmentId":114189203,"attachmentType":"pdf","work_url":"https://www.academia.edu/118602597/The_role_of_cancer_stem_cells_in_tumor_heterogeneity_and_resistance_to_therapy","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/118602597/The_role_of_cancer_stem_cells_in_tumor_heterogeneity_and_resistance_to_therapy"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="6" data-entity-id="62095306" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/62095306/Cancer_Stem_Cells_Key_Players_in_Tumor_Relapse">Cancer Stem Cells—Key Players in Tumor Relapse</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="29364366" href="https://independent.academia.edu/PatriziaLimonta">Patrizia Limonta</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Cancers</p><p class="ds-related-work--abstract ds2-5-body-sm">Tumor relapse and treatment failure are unfortunately common events for cancer patients, thus often rendering cancer an uncurable disease. Cancer stem cells (CSCs) are a subset of cancer cells endowed with tumor-initiating and self-renewal capacity, as well as with high adaptive abilities. Altogether, these features contribute to CSC survival after one or multiple therapeutic approaches, thus leading to treatment failure and tumor progression/relapse. Thus, elucidating the molecular mechanisms associated with stemness-driven resistance is crucial for the development of more effective drugs and durable responses. This review will highlight the mechanisms exploited by CSCs to overcome different therapeutic strategies, from chemo- and radiotherapies to targeted therapies and immunotherapies, shedding light on their plasticity as an insidious trait responsible for their adaptation/escape. Finally, novel CSC-specific approaches will be described, providing evidence of their preclinical a...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Cancer Stem Cells—Key Players in Tumor Relapse","attachmentId":74950055,"attachmentType":"pdf","work_url":"https://www.academia.edu/62095306/Cancer_Stem_Cells_Key_Players_in_Tumor_Relapse","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/62095306/Cancer_Stem_Cells_Key_Players_in_Tumor_Relapse"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="7" data-entity-id="97895062" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/97895062/Cancer_stem_cells_a_major_culprit_of_intra_tumor_heterogeneity">Cancer stem cells: a major culprit of intra-tumor heterogeneity</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="260040609" href="https://independent.academia.edu/FaizaNaz14">Faiza Naz</a></div><p class="ds-related-work--metadata ds2-5-body-xs">American journal of cancer research, 2021</p><p class="ds-related-work--abstract ds2-5-body-sm">Cancer is recognized as a preeminent factor of the world&#39;s mortality. Although various modalities have been designed to cure this life-threatening ailment, a significant impediment in the effective output of cancer treatment is heterogeneity. Cancer is characterized as a heterogeneous health disorder that comprises a distinct group of transformed cells to assist anomalous proliferation of affected cells. Cancer stem cells (CSCs) are a leading cause of cancer heterogeneity that is continually transformed by cellular extrinsic and intrinsic factors. They intensify neoplastic cells aggressiveness by strengthening their dissemination, relapse and therapy resistance. Considering this viewpoint, in this review article we have discussed some intrinsic (transcription factors, cell signaling pathways, genetic alterations, epigenetic modifications, non-coding RNAs (ncRNAs) and epitranscriptomics) and extrinsic factors (tumor microenvironment (TME)) that contribute to CSC heterogeneity and...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Cancer stem cells: a major culprit of intra-tumor heterogeneity","attachmentId":99394361,"attachmentType":"pdf","work_url":"https://www.academia.edu/97895062/Cancer_stem_cells_a_major_culprit_of_intra_tumor_heterogeneity","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/97895062/Cancer_stem_cells_a_major_culprit_of_intra_tumor_heterogeneity"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="8" data-entity-id="106452231" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/106452231/Intrinsic_and_Extrinsic_Factors_Impacting_Cancer_Stemness_and_Tumor_Progression">Intrinsic and Extrinsic Factors Impacting Cancer Stemness and Tumor Progression</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="276663329" href="https://independent.academia.edu/cinziaallegrucci">cinzia allegrucci</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Cancers, 2022</p><p class="ds-related-work--abstract ds2-5-body-sm">Tumor heterogeneity represents an important limitation to the development of effective cancer therapies. The presence of cancer stem cells (CSCs) and their differentiation hierarchies contribute to cancer complexity and confer tumors the ability to grow, resist treatment, survive unfavorable conditions, and invade neighboring and distant tissues. A large body of research is currently focusing on understanding the properties of CSCs, including their cellular and molecular origin, as well as their biological behavior in different tumor types. In turn, this knowledge informs strategies for targeting these tumor initiating cells and related cancer stemness. Cancer stemness is modulated by the tumor microenvironment, which influences CSC function and survival. Several advanced in vitro models are currently being developed to study cancer stemness in order to advance new knowledge of the key molecular pathways involved in CSC self-renewal and dormancy, as well as to mimic the complexity o...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Intrinsic and Extrinsic Factors Impacting Cancer Stemness and Tumor Progression","attachmentId":105646028,"attachmentType":"pdf","work_url":"https://www.academia.edu/106452231/Intrinsic_and_Extrinsic_Factors_Impacting_Cancer_Stemness_and_Tumor_Progression","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/106452231/Intrinsic_and_Extrinsic_Factors_Impacting_Cancer_Stemness_and_Tumor_Progression"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="9" data-entity-id="60438135" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/60438135/Recent_Advances_in_Cancer_Plasticity_Cellular_Mechanisms_Surveillance_Strategies_and_Therapeutic_Optimization">Recent Advances in Cancer Plasticity: Cellular Mechanisms, Surveillance Strategies, and Therapeutic Optimization</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="53558269" href="https://pisa.academia.edu/CristianScatena">Cristian Scatena</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Frontiers in Oncology</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Recent Advances in Cancer Plasticity: Cellular Mechanisms, Surveillance Strategies, and Therapeutic Optimization","attachmentId":73885364,"attachmentType":"pdf","work_url":"https://www.academia.edu/60438135/Recent_Advances_in_Cancer_Plasticity_Cellular_Mechanisms_Surveillance_Strategies_and_Therapeutic_Optimization","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/60438135/Recent_Advances_in_Cancer_Plasticity_Cellular_Mechanisms_Surveillance_Strategies_and_Therapeutic_Optimization"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div></div></div><div class="ds-sticky-ctas--wrapper js-loswp-sticky-ctas hidden"><div class="ds-sticky-ctas--grid-container"><div class="ds-sticky-ctas--container"><button class="ds2-5-button js-swp-download-button" data-signup-modal="{"location":"continue-reading-button--sticky-ctas","attachmentId":62374440,"attachmentType":"pdf","workUrl":null}">See full PDF</button><button class="ds2-5-button ds2-5-button--secondary js-swp-download-button" data-signup-modal="{"location":"download-pdf-button--sticky-ctas","attachmentId":62374440,"attachmentType":"pdf","workUrl":null}"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span>Download PDF</button></div></div></div><div class="ds-below-fold--grid-container"><div class="ds-work--container js-loswp-embedded-document"><div class="attachment_preview" data-attachment="Attachment_62374440" style="display: none"><div class="js-scribd-document-container"><div class="scribd--document-loading js-scribd-document-loader" style="display: block;"><img alt="Loading..." src="//a.academia-assets.com/images/loaders/paper-load.gif" /><p>Loading Preview</p></div></div><div style="text-align: center;"><div class="scribd--no-preview-alert js-preview-unavailable"><p>Sorry, preview is currently unavailable. 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