Significance of circulating tumor cells in lung cancer: a narrative review
Gerhard Hamilton, Barbara H. Rath, Sandra Stickler
Abstract
Background 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 of unique SCLC CTC lines. Methods: , 2022 using the following key words: "SCLC", "NSCLC", "CTC" and "Angiogenesis" and supplemented by data from our own work. Key Content and Findings: and are suggested to extravasate by physical force. The rate-limiting step of the shedding of CTCs is 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 rarity of CTCs in NSCLC versus SCLC. Conclusions: 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 prognosis.