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The review addresses why CTC dissemination mechanisms remain incompletely defined, especially the steps of intravasation, survival in circulation, and extravasation that generate metastases in lung cancer. It synthesizes evidence from studies and methods panel work to explain how CTC entry and release relate to neoangiogenesis and angiogenic switching, with implications for metastatic potential and biomarker value.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/significance-of-circulating-tumor-cells-in-lung-cancer-a-narrative-review/405660/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/significance-of-circulating-tumor-cells-in-lung-cancer-a-narrative-review/405660.png","ImageObject",300,407,{"name":92,"@type":93},"River Wang","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-28",true,{"@type":102,"interactionType":103,"userInteractionCount":29},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What role do circulating tumor cells (CTCs) play in lung cancer management?","Question",{"text":112,"@type":113},"CTCs are used as a “liquid biopsy” approach to support tumor detection, prognosis assessment, and evaluation of response to therapy.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Which unresolved biological steps does the review focus on?",{"text":117,"@type":113},"It highlights incomplete characterization of intravasation, survival in the circulation, and extravasation at secondary sites that together establish metastases.",{"name":119,"@type":110,"acceptedAnswer":120},"What angiogenesis-related mechanism is proposed to influence CTC shedding and rarity in NSCLC?",{"text":121,"@type":113},"The review links CTC shedding to irregular and leaky tumor vessels and, for SCLC, also to vessels formed by vasculogenic mimicry; it further suggests that lower microvessel density in NSCLC can explain fewer CTCs compared with SCLC.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},405660,1790846320,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":29,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},1099514067438,"https://ap-avatar.wpscdn.com/avatar/100002539ee87300030?x-image-process=image/resize,m_fixed,w_180,h_180&k=1780474512215547542","Significance of circulating tumor cells in lung cancer: a narrative review  \nGerhard Hamilton, Barbara Rath, Sandra Stickler  \nInstitute of Pharmacology, Medical University of Vienna, Vienna, Austria  \nContributions: (I) Conception and design: G Hamilton; (II) Administrative support: S Stickler; (III) Provision of study materials or patients: B Rath, S Stickler; (IV) Collection and assembly of data: All authors; (V) Data analysis and interpretation: G Hamilton; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.  \nCorrespondence to: Gerhard Hamilton, PhD. Institute of Pharmacology, Medical University of Vienna, Vienna, Austria.  \nEmail: [gerhard.hamilton@meduniwien.ac.at](gerhard.hamilton@meduniwien.ac.at).  \nBackground and Objective: In cancer patients, circulating tumor cells (CTCs) are employed as “Liquid Biopsy” for tumor detection, prognosis and assessment of the response to therapy. CTCs are responsible for tumor dissemination but the mechanisms involved in intravasation, survival in the circulation and extravasation at secondary sites to establish metastases are not fully characterized. In lung cancer patients, CTCs are present in very high numbers in small cell lung cancer (SCLC) that is found disseminated in most patients upon first presentation and has a dismal prognosis. This review aims at the discussion of recent work on metastatic SCLC and novel insights into the process of dissemination derived from the access to a panel  \nof unique SCLC CTC lines.  \nMethods: PubMed and Euro PMC were searched from January 1st, 2015 to September 23th, 2022 using the  \nfollowing key words: “SCLC”,“NSCLC”,“CTC” and “Angiogenesis” and supplemented by data from our  \nown work.  \nKey Content and Findings: Experimental and clinical data indicate that the intravasation of single, apoptotic or clustered CTCs occur via leaky neoangiogenetic vessels in the tumor core and not via crossing of the adjacent tumor stroma after EMT. Furthermore, in lung cancer only EpCAM-positive CTCs have been found to have prognostic impact. All our established SCLC CTC lines form spontaneously EpCAMpositive large and chemoresistant spheroids (tumorospheres) that may become trapped in microvessels in vivo and are suggested to extravasate by physical force. The rate-limiting step of the shedding of CTCsis most likely the presence of irregular and leaky tumor vessels or in case of SCLC, also via vessels formed by vasculogenic mimicry. Therefore, lower microvessel densities (MVD) in NSCLC can explain the relative  \nrarity ofCTCs in NSCLC versus SCLC.  \nConclusions: The detection of CTCs lacks standardized techniques, is difficult in non-metastatic patients and important cell biological mechanisms of dissemination need still to be resolved, especially in respect to the actual metastasis-inducing cells. Expression of VEGF and the MVD are key prognostic indicators for tumors and ultimately, enumeration of CTCs seems to reflect neoangiogenetic vascular supply of tumors and  \nprognosis.  \nKeywords: Lung cancer; non-small cell lung cancer (NSCLC); small cell lung cancer (SCLC); circulating tumor  \ncells; angiogenesis; metastasis  \nSubmitted Sep 30, 2022. Accepted for publication Mar 07, 2023. Published online Mar 29, 2023.  \ndoi: 10.21037/tlcr-22-712  \nView this article at: [https://dx.doi.org/10.21037/tlcr-22-712](https://dx.doi.org/10.21037/tlcr-22-712)  \n© Translational Lung Cancer Research. All rights reserved. Transl Lung Cancer Res 2023;12(4):877-894 | [https://dx.doi.org/10.21037/tlcr-22-712](https://dx.doi.org/10.21037/tlcr-22-712)  \n878 Hamilton et al. Lung cancer and CTCs  \nIntroduction  \nAlthough great progress has been made in the treatment of cancer patients, metastatic disease is frequently not amenable to any further therapy (1,2) . Metastasis takes place in several steps comprising cancer cell intravasation, migration, extravasation and establishment of secondary lesions (Figure 1) . Because the course of tumor metasta","cbCailceOwHQ8rEs","https://ap.wps.com/l/cbCailceOwHQ8rEs","pdf",1704851,18,"English","# Background and Objective\n# Methods\n# Key Content and Findings\n# Conclusions\n# Introduction","[{\"question\":\"What role do circulating tumor cells (CTCs) play in lung cancer management?\",\"answer\":\"CTCs are used as a “liquid biopsy” approach to support tumor detection, prognosis assessment, and evaluation of response to therapy.\"},{\"question\":\"Which unresolved biological steps does the review focus on?\",\"answer\":\"It highlights incomplete characterization of intravasation, survival in the circulation, and extravasation at secondary sites that together establish metastases.\"},{\"question\":\"What angiogenesis-related mechanism is proposed to influence CTC shedding and rarity in NSCLC?\",\"answer\":\"The review links CTC shedding to irregular and leaky tumor vessels and, for SCLC, also to vessels formed by vasculogenic mimicry; it further suggests that lower microvessel density in NSCLC can explain fewer CTCs compared with SCLC.\"}]","Significance of circulating tumor cells in lung cancer - A narrative review | PDF",1790561312,45]