SCLC: Epidemiology, Risk Factors, Genetic Susceptibility, Molecular Pathology, Screening, and Early Detection

Overview

Journal J Thorac Oncol

Publisher Elsevier

Specialties Oncology
Pulmonary Medicine

Date 2022 Oct 15

PMID 36243387

Authors

Qian Wang

Zeynep H Gumus

Cristina Colarossi

Lorenzo Memeo

Xintong Wang

Chung Yin Kong

Paolo Boffetta

Affiliations

Soon will be listed here.

Abstract

We review research regarding the epidemiology, risk factors, genetic susceptibility, molecular pathology, and early detection of SCLC, a deadly tumor that accounts for 14% of lung cancers. We first summarize the changing incidences of SCLC globally and in the United States among males and females. We then review the established risk factor (i.e., tobacco smoking) and suspected nonsmoking-related risk factors for SCLC, and emphasize the importance of continued effort in tobacco control worldwide. Review of genetic susceptibility and molecular pathology suggests different molecular pathways in SCLC development compared with other types of lung cancer. Last, we comment on the limited utility of low-dose computed tomography screening in SCLC and on several promising blood-based molecular biomarkers as potential tools in SCLC early detection.

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References

Reitsma M, Flor L, Mullany E, Gupta V, Hay S, Gakidou E . Spatial, temporal, and demographic patterns in prevalence of smoking tobacco use and initiation among young people in 204 countries and territories, 1990-2019. Lancet Public Health. 2021; 6(7):e472-e481. PMC: 8251503. DOI: 10.1016/S2468-2667(21)00102-X. View

Pan L, Morton J, Mbulo L, Dean A, Ahluwalia I . Electronic cigarette use among adults in 14 countries: A cross-sectional study. EClinicalMedicine. 2022; 47:101401. PMC: 9046112. DOI: 10.1016/j.eclinm.2022.101401. View

Pleasants R, Rivera M, Tilley S, Bhatt S . Both Duration and Pack-Years of Tobacco Smoking Should Be Used for Clinical Practice and Research. Ann Am Thorac Soc. 2020; 17(7):804-806. PMC: 7405110. DOI: 10.1513/AnnalsATS.202002-133VP. View

Fernandes M, Sousa C, Pereira Reis J, Cruz-Martins N, Moura C, Guimaraes S . Liquid Biopsy for Disease Monitoring in Non-Small Cell Lung Cancer: The Link between Biology and the Clinic. Cells. 2021; 10(8). PMC: 8394732. DOI: 10.3390/cells10081912. View

Tlemsani C, Takahashi N, Pongor L, Rajapakse V, Tyagi M, Wen X . Whole-exome sequencing reveals germline-mutated small cell lung cancer subtype with favorable response to DNA repair-targeted therapies. Sci Transl Med. 2021; 13(578). PMC: 8489678. DOI: 10.1126/scitranslmed.abc7488. View

Dingemans A, Fruh M, Ardizzoni A, Besse B, Faivre-Finn C, Hendriks L . Small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2021; 32(7):839-853. PMC: 9464246. DOI: 10.1016/j.annonc.2021.03.207. View

Schaffer B, Park K, Yiu G, Conklin J, Lin C, Burkhart D . Loss of p130 accelerates tumor development in a mouse model for human small-cell lung carcinoma. Cancer Res. 2010; 70(10):3877-83. PMC: 2873158. DOI: 10.1158/0008-5472.CAN-09-4228. View

Jia D, Augert A, Kim D, Eastwood E, Wu N, Ibrahim A . Loss Drives Small Cell Lung Cancer and Increases Sensitivity to HDAC Inhibition. Cancer Discov. 2018; 8(11):1422-1437. PMC: 6294438. DOI: 10.1158/2159-8290.CD-18-0385. View

Varghese A, Zakowski M, Yu H, Won H, Riely G, Krug L . Small-cell lung cancers in patients who never smoked cigarettes. J Thorac Oncol. 2014; 9(6):892-6. PMC: 4199745. DOI: 10.1097/JTO.0000000000000142. View

10.

Gohagan J, Marcus P, Fagerstrom R, Pinsky P, Kramer B, Prorok P . Final results of the Lung Screening Study, a randomized feasibility study of spiral CT versus chest X-ray screening for lung cancer. Lung Cancer. 2004; 47(1):9-15. DOI: 10.1016/j.lungcan.2004.06.007. View

11.

Attar N, Kurdistani S . Exploitation of EP300 and CREBBP Lysine Acetyltransferases by Cancer. Cold Spring Harb Perspect Med. 2016; 7(3). PMC: 5334244. DOI: 10.1101/cshperspect.a026534. View

12.

Tanaka F, Yoneda K, Kondo N, Hashimoto M, Takuwa T, Matsumoto S . Circulating tumor cell as a diagnostic marker in primary lung cancer. Clin Cancer Res. 2009; 15(22):6980-6. DOI: 10.1158/1078-0432.CCR-09-1095. View

13.

Cuffe S, Moua T, Summerfield R, Roberts H, Jett J, Shepherd F . Characteristics and outcomes of small cell lung cancer patients diagnosed during two lung cancer computed tomographic screening programs in heavy smokers. J Thorac Oncol. 2011; 6(4):818-22. DOI: 10.1097/JTO.0b013e31820c2f2e. View

14.

Hussain M, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S . Survival with Olaparib in Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2020; 383(24):2345-2357. DOI: 10.1056/NEJMoa2022485. View

15.

Hegmann K, Fraser A, Keaney R, Moser S, Nilasena D, Sedlars M . The effect of age at smoking initiation on lung cancer risk. Epidemiology. 1993; 4(5):444-8. DOI: 10.1097/00001648-199309000-00010. View

16.

Kneip C, Schmidt B, Seegebarth A, Weickmann S, Fleischhacker M, Liebenberg V . SHOX2 DNA methylation is a biomarker for the diagnosis of lung cancer in plasma. J Thorac Oncol. 2011; 6(10):1632-8. DOI: 10.1097/JTO.0b013e318220ef9a. View

17.

Hung R, McKay J, Gaborieau V, Boffetta P, Hashibe M, Zaridze D . A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25. Nature. 2008; 452(7187):633-7. DOI: 10.1038/nature06885. View

18.

Mazzone P, Wang X, Han X, Choi H, Seeley M, Scherer R . Evaluation of a Serum Lung Cancer Biomarker Panel. Biomark Insights. 2018; 13:1177271917751608. PMC: 5772503. DOI: 10.1177/1177271917751608. View

19.

Wang J, Zhou C, Yao W, Wang Q, Min X, Chen G . Adebrelimab or placebo plus carboplatin and etoposide as first-line treatment for extensive-stage small-cell lung cancer (CAPSTONE-1): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2022; 23(6):739-747. DOI: 10.1016/S1470-2045(22)00224-8. View

20.

Ten Haaf K, van Rosmalen J, de Koning H . Lung cancer detectability by test, histology, stage, and gender: estimates from the NLST and the PLCO trials. Cancer Epidemiol Biomarkers Prev. 2014; 24(1):154-61. PMC: 4357842. DOI: 10.1158/1055-9965.EPI-14-0745. View