Significance of circulating tumor cells in lung cancer: a narrative review

Hamilton, Gerhard; Rath, Barbara H.; Stickler, Sandra

doi:10.21037/tlcr-22-712

Cited by 6 publications

(4 citation statements)

References 173 publications

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“…After DNA amplification, it is now possible to directly, qualitatively and quantitatively examine ctDNA using well-established detection techniques such as NGS and digital PCR owing to the rapid improvement of DNA sequencing technology. The therapeutic application value of ctDNA has to be further validated through many pertinent clinical trials and standardize the detection process ( 209 ). EVs have generated much attention in liquid biopsy of cancer as a possible biomarker for cancer detection.…”

Section: Discussionmentioning

confidence: 99%

Research progress of CTC, ctDNA, and EVs in cancer liquid biopsy

Wang,

Lin

et al. 2024

Front. Oncol.

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Circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and extracellular vehicles (EVs) have received significant attention in recent times as emerging biomarkers and subjects of transformational studies. The three main branches of liquid biopsy have evolved from the three primary tumor liquid biopsy detection targets—CTC, ctDNA, and EVs—each with distinct benefits. CTCs are derived from circulating cancer cells from the original tumor or metastases and may display global features of the tumor. ctDNA has been extensively analyzed and has been used to aid in the diagnosis, treatment, and prognosis of neoplastic diseases. EVs contain tumor-derived material such as DNA, RNA, proteins, lipids, sugar structures, and metabolites. The three provide different detection contents but have strong complementarity to a certain extent. Even though they have already been employed in several clinical trials, the clinical utility of three biomarkers is still being studied, with promising initial findings. This review thoroughly overviews established and emerging technologies for the isolation, characterization, and content detection of CTC, ctDNA, and EVs. Also discussed were the most recent developments in the study of potential liquid biopsy biomarkers for cancer diagnosis, therapeutic monitoring, and prognosis prediction. These included CTC, ctDNA, and EVs. Finally, the potential and challenges of employing liquid biopsy based on CTC, ctDNA, and EVs for precision medicine were evaluated.

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Section: Discussionmentioning

confidence: 99%

Research progress of CTC, ctDNA, and EVs in cancer liquid biopsy

Wang,

Lin

et al. 2024

Front. Oncol.

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“…The main cause of death in cancer patients is metastasis. A number of studies have shown that circulating clusters of tumor cells are associated with a greater risk of metastasis and relapse in NSCLC patients than single circulating tumor cells[ 46 - 48 ]. Previously, we proposed a possible mechanism for the formation of tumor cell clusters in tumor MVs[ 21 ].…”

Section: Discussionmentioning

confidence: 99%

“…Importantly, increasing evidence suggests that intravasation of single, apoptotic or clusters of tumor cells can occur via leaky neoangiogenetic vessels in the tumor core and not by crossing the adjacent tumor stroma after EMT[ 48 ]. Hamilton et al [ 48 ] emphasized that some tumor emboli may be located in blind nonfunctioning tumor vessels, which may limit their entry into the bloodstream. We believe that these data indirectly confirm the possibility of the formation of circulating clusters of tumor cells by the mechanism of cavity-type angiogenesis described above.…”

Section: Discussionmentioning

confidence: 99%

Different types of tumor microvessels in stage I-IIIA squamous cell lung cancer and their clinical significance

Senchukova,

Kalinin,

Volchenko

2024

World J Clin Oncol

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BACKGROUND Lung cancer (LC) is the leading cause of morbidity and mortality among malignant neoplasms. Improving the diagnosis and treatment of LC remains an urgent task of modern oncology. Previously, we established that in gastric, breast and cervical cancer, tumor microvessels (MVs) differ in morphology and have different prognostic significance. The connection between different types of tumor MVs and the progression of LC is not well understood. AIM To evaluate the morphological features and clinical significance of tumor MVs in lung squamous cell carcinoma (LUSC). METHODS A single-center retrospective cohort study examined medical records and archival paraffin blocks of 62 and 180 patients with stage I-IIIA LUSC in the training and main cohorts, respectively. All patients underwent radical surgery (R0) at the Orenburg Regional Cancer Clinic from May/20/2009 to December/14/2021. Tumor sections were routinely processed, and routine Mayer's hematoxylin and eosin staining and immunohistochemical staining for cluster of differentiation 34 (CD34), podoplanin, Snail and hypoxia-inducible factor-1 alpha were performed. The morphological features of different types of tumor MVs, tumor parenchyma and stroma were studied according to clinicopathological characteristics and LUSC prognosis. Statistical analysis was performed using Statistica 10.0 software. Univariate and multivariate logistic regression analyses were performed to identify potential risk factors for LUSC metastasis to regional lymph nodes (RLNs) and disease recurrence. Receiver operating characteristic curves were constructed to discriminate between patients with and without metastases in RLNs and those with and without disease recurrence. The effectiveness of the predictive models was assessed by the area under the curve. Survival was analyzed using the Kaplan-Meier method. The log-rank test was used to compare survival curves between patient subgroups. A value of P < 0.05 was considered to indicate statistical significance. RESULTS Depending on the morphology, we classified tumor vessels into the following types: normal MVs, dilated capillaries (DCs), atypical DCs, DCs with weak expression of CD34, "contact-type" DCs, structures with partial endothelial linings, capillaries in the tumor solid component and lymphatic vessels in lymphoid and polymorphocellular infiltrates. We also evaluated the presence of loose, fine fibrous connective tissue (LFFCT) and retraction clefts in the tumor stroma, tumor spread into the alveolar air spaces (AASs) and fragmentation of the tumor solid component. According to multivariate analysis, the independent predictors of LUSC metastasis in RLNs were central tumor location (P < 0.00001), the presence of retraction clefts (P = 0.003), capillaries in the tumor solid component (P = 0.023) and fragmentation in the tumor solid component (P = 0.009), whereas the independent predictors of LUSC recurrence were tumor grade 3 (G3) (P = 0.001), stage N2 (P = 0.016), the presence of LFFCT in the tumor stroma (P < 0.00001), fragmentation of the tumor solid component (P = 0.0001), and the absence of tumor spread through the AASs (P = 0.0083). CONCLUSION The results obtained confirm the correctness of our previously proposed classification of different types of tumor vessels and may contribute to improving the diagnosis and treatment of LUSC.

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“…CTCs can enter the circulation through irregular tumor vessels as single cells or circulating tumor micro-emboli [44]. Certainly, the small cell size (about 8 µm) and high pulmonary blood perfusion are crucial factors for the spread of CTCs [45,46]. It has been shown that although clusters of CTCs are rare in peripheral blood, they have greater metastatic potential than single CTCs [47] and that, in contrast, patients who had no clusters at baseline had significantly better progression-free survival (PFS) (8.2 vs. 4.6 months, p < 0.001) and OS (10.4 vs. 4.3 months, p < 0.001) than patients who had clusters of CTCs at the same time-point [44].…”

Section: Circulating Tumor Cells (Ctcs)mentioning

confidence: 99%

Small-Cell Lung Cancer: Is Liquid Biopsy a New Tool Able to Predict the Efficacy of Immunotherapy?

Fasano,

Serratì,

Rafaschieri

et al. 2024

Biomolecules

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Small-cell lung cancer (SCLC) cases represent approximately 15% of all lung cancer cases, remaining a recalcitrant malignancy with poor survival and few treatment options. In the last few years, the addition of immunotherapy to chemotherapy improved clinical outcomes compared to chemotherapy alone, resulting in the current standard of care for SCLC. However, the advantage of immunotherapy only applies to a few SCLC patients, and predictive biomarkers selection are lacking for SCLC. In particular, due to some features of SCLC, such as high heterogeneity, elevated cell plasticity, and low-quality tissue samples, SCLC biopsies cannot be used as biomarkers. Therefore, the characterization of the tumor and, subsequently, the selection of an appropriate therapeutic combination may benefit greatly from liquid biopsy. Soluble factors, circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and extracellular vesicles (EVs) are now useful tools in the characterization of SCLC. This review summarizes the most recent data on biomarkers detectable with liquid biopsy, emphasizing their role in supporting tumor detection and their potential role in SCLC treatment choice.

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Significance of circulating tumor cells in lung cancer: a narrative review

Cited by 6 publications

References 173 publications

Research progress of CTC, ctDNA, and EVs in cancer liquid biopsy

Research progress of CTC, ctDNA, and EVs in cancer liquid biopsy

Different types of tumor microvessels in stage I-IIIA squamous cell lung cancer and their clinical significance

Small-Cell Lung Cancer: Is Liquid Biopsy a New Tool Able to Predict the Efficacy of Immunotherapy?

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