Advances in the Role of Circulating Tumor Cell Heterogeneity in Metastatic Small Cell Lung Cancer

Overview

Journal Cancer Innov

Specialty Biomedical Engineering

Date 2024 Jul 1

PMID 38946931

Authors

Qunxia Wang

Li-Ming Tan

Affiliations

Soon will be listed here.

Abstract

Small cell lung cancer (SCLC), a highly aggressive malignancy, is rapidly at an extensive stage once diagnosed and is one of the leading causes of death from malignancy. In the past decade, the treatment of SCLC has largely remained unchanged, and chemotherapy remains the cornerstone of SCLC treatment. The therapeutic value of adding immune checkpoint inhibitors to chemotherapy for SCLC is low, and only a few SCLC patients have shown a response to immune checkpoint inhibitors. Circulating tumor cells (CTCs) are tumor cells shed from solid tumor masses into the peripheral circulation and are key to tumor metastasis. Single-cell sequencing has revealed that the genetic profiles of individual CTCs are highly heterogeneous and contribute to the poor outcome and prognosis of SCLC patients. Theoretically, phenotypic analysis of CTCs may be able to predict the diagnostic significance of new potential targets for metastatic tumors. In this paper, we will discuss in depth the heterogeneity of CTCs in SCLC and the value of CTCs for the diagnosis and prognosis of SCLC and as relevant tumor markers in metastatic SCLC.

Citing Articles

PTPMT1 inhibition induces apoptosis and growth arrest of human SCLC cells by disrupting mitochondrial metabolism.

Liu X, Sun Y, Gao C, Sun H, Tian F, Xiao F Transl Cancer Res. 2025; 13(12):6956-6969.

PMID: 39816544 PMC: 11730198. DOI: 10.21037/tcr-2024-2379.

References

Normanno N, Rossi A, Morabito A, Signoriello S, Bevilacqua S, Di Maio M . Prognostic value of circulating tumor cells' reduction in patients with extensive small-cell lung cancer. Lung Cancer. 2014; 85(2):314-9. DOI: 10.1016/j.lungcan.2014.05.002. View

Chen W, Allen S, Reka A, Qian W, Han S, Zhao J . Nanoroughened adhesion-based capture of circulating tumor cells with heterogeneous expression and metastatic characteristics. BMC Cancer. 2016; 16:614. PMC: 4977622. DOI: 10.1186/s12885-016-2638-x. View

Park S, Wong D, Ooi C, Kurtz D, Vermesh O, Aalipour A . Molecular profiling of single circulating tumor cells from lung cancer patients. Proc Natl Acad Sci U S A. 2016; 113(52):E8379-E8386. PMC: 5206556. DOI: 10.1073/pnas.1608461113. View

Powell A, Talasaz A, Zhang H, Coram M, Reddy A, Deng G . Single cell profiling of circulating tumor cells: transcriptional heterogeneity and diversity from breast cancer cell lines. PLoS One. 2012; 7(5):e33788. PMC: 3346739. DOI: 10.1371/journal.pone.0033788. View

Yu T, Wang C, Xie M, Zhu C, Shu Y, Tang J . Heterogeneity of CTC contributes to the organotropism of breast cancer. Biomed Pharmacother. 2021; 137:111314. DOI: 10.1016/j.biopha.2021.111314. View

Stewart C, Gay C, Xi Y, Sivajothi S, Sivakamasundari V, Fujimoto J . Single-cell analyses reveal increased intratumoral heterogeneity after the onset of therapy resistance in small-cell lung cancer. Nat Cancer. 2021; 1:423-436. PMC: 7842382. DOI: 10.1038/s43018-019-0020-z. View

Rudin C, Poirier J, Byers L, Dive C, Dowlati A, George J . Molecular subtypes of small cell lung cancer: a synthesis of human and mouse model data. Nat Rev Cancer. 2019; 19(5):289-297. PMC: 6538259. DOI: 10.1038/s41568-019-0133-9. View

Fiorelli A, Accardo M, Carelli E, Angioletti D, Santini M, Di Domenico M . Circulating Tumor Cells in Diagnosing Lung Cancer: Clinical and Morphologic Analysis. Ann Thorac Surg. 2015; 99(6):1899-905. DOI: 10.1016/j.athoracsur.2014.11.049. View

Owen D, Giffin M, Bailis J, Smit M, Carbone D, He K . DLL3: an emerging target in small cell lung cancer. J Hematol Oncol. 2019; 12(1):61. PMC: 6582566. DOI: 10.1186/s13045-019-0745-2. View

10.

Carter L, Rothwell D, Mesquita B, Smowton C, Leong H, Fernandez-Gutierrez F . Molecular analysis of circulating tumor cells identifies distinct copy-number profiles in patients with chemosensitive and chemorefractory small-cell lung cancer. Nat Med. 2016; 23(1):114-119. DOI: 10.1038/nm.4239. View

11.

Lin M, Chen J, Lu Y, Zhang Y, Song J, Hou S . Nanostructure embedded microchips for detection, isolation, and characterization of circulating tumor cells. Acc Chem Res. 2014; 47(10):2941-50. PMC: 4204926. DOI: 10.1021/ar5001617. View

12.

Alix-Panabieres C, Pantel K . Liquid Biopsy: From Discovery to Clinical Application. Cancer Discov. 2021; 11(4):858-873. DOI: 10.1158/2159-8290.CD-20-1311. View

13.

Magbanua M, Rugo H, Wolf D, Hauranieh L, Roy R, Pendyala P . Expanded Genomic Profiling of Circulating Tumor Cells in Metastatic Breast Cancer Patients to Assess Biomarker Status and Biology Over Time (CALGB 40502 and CALGB 40503, Alliance). Clin Cancer Res. 2018; 24(6):1486-1499. PMC: 5856614. DOI: 10.1158/1078-0432.CCR-17-2312. View

14.

Deng G, Krishnakumar S, Powell A, Zhang H, Mindrinos M, Telli M . Single cell mutational analysis of PIK3CA in circulating tumor cells and metastases in breast cancer reveals heterogeneity, discordance, and mutation persistence in cultured disseminated tumor cells from bone marrow. BMC Cancer. 2014; 14:456. PMC: 4071027. DOI: 10.1186/1471-2407-14-456. View

15.

Lozar T, Jesenko T, Kloboves Prevodnik V, Cemazar M, Hosta V, Jericevic A . Preclinical and Clinical Evaluation of Magnetic-Activated Cell Separation Technology for CTC Isolation in Breast Cancer. Front Oncol. 2020; 10:554554. PMC: 7522616. DOI: 10.3389/fonc.2020.554554. View

16.

Harmsma M, Schutte B, Ramaekers F . Serum markers in small cell lung cancer: opportunities for improvement. Biochim Biophys Acta. 2013; 1836(2):255-72. DOI: 10.1016/j.bbcan.2013.06.002. View

17.

Nicholson A, Chansky K, Crowley J, Beyruti R, Kubota K, Turrisi A . The International Association for the Study of Lung Cancer Lung Cancer Staging Project: Proposals for the Revision of the Clinical and Pathologic Staging of Small Cell Lung Cancer in the Forthcoming Eighth Edition of the TNM Classification for Lung.... J Thorac Oncol. 2016; 11(3):300-11. DOI: 10.1016/j.jtho.2015.10.008. View

18.

Barr J, Chudasama D, Rice A, Karteris E, Anikin V . Lack of association between Screencell-detected circulating tumour cells and long-term survival of patients undergoing surgery for non-small cell lung cancer: A pilot clinical study. Mol Clin Oncol. 2020; 12(3):191-195. PMC: 7016525. DOI: 10.3892/mco.2020.1981. View

19.

Huang Q, Wang F, Yuan C, He Z, Rao L, Cai B . Gelatin Nanoparticle-Coated Silicon Beads for Density-Selective Capture and Release of Heterogeneous Circulating Tumor Cells with High Purity. Theranostics. 2018; 8(6):1624-1635. PMC: 5858171. DOI: 10.7150/thno.23531. View

20.

Sgambato A, Casaluce F, Maione P, Rossi A, Sacco P, Panzone F . Medical treatment of small cell lung cancer: state of the art and new development. Expert Opin Pharmacother. 2013; 14(15):2019-31. DOI: 10.1517/14656566.2013.823401. View