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Review
. 2021 Apr 6;13(7):1723.
doi: 10.3390/cancers13071723.

Small Cell Lung Cancer: State of the Art of the Molecular and Genetic Landscape and Novel Perspective

Valeria Denninghoff  1 , Alessandro Russo  2   3 , Diego de Miguel-Pérez  2 , Umberto Malapelle  4 , Amin Benyounes  5 , Allison Gittens  2 , Andres Felipe Cardona  6   7   8 , Christian Rolfo  2
Affiliations
Review

Small Cell Lung Cancer: State of the Art of the Molecular and Genetic Landscape and Novel Perspective

Valeria Denninghoff et al. Cancers (Basel). .

Abstract

Small cell lung cancer (SCLC) is a highly proliferative lung cancer that is not amenable to surgery in most cases due to the high metastatic potential. Precision medicine has not yet improved patients' survival due to the lack of actionable mutations. Intra- and intertumoral heterogeneity allow the neoplasms to adapt to various microenvironments and treatments. Further studying this heterogeneous cancer might yield the discovery of actionable mutations. First-line SCLC treatment has added immunotherapy to its armamentarium. There has been renewed interest in SCLC, and numerous clinical trials are underway with novel therapeutic approaches. Understanding the molecular and genetic landscape of this heterogeneous and lethal disease will pave the way for novel drug development.

Keywords: gene pathway; pathobiology; small cell lung cancer; targeted therapy.

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Conflict of interest statement

V.D. received personal fees (as consultant and/or speaker bureau) from Bristol, Amgen, Novartis, MSD, and Roche, and their research is sponsored by BMS, Novartis, Amgen, AstraZeneca, and Roche, unrelated to the current work. A.F.C. discloses financial research support from Merck Sharp & Dohme, Boehringer Ingelheim, Roche, Bristol-Myers Squibb, and the Foundation for Clinical and Applied Cancer Research (FICMAC); additionally, he was linked and received honoraria as an advisor, participated in speakers’ bureau, and gave expert testimony to Merck Sharp & Dohme, Boehringer Ingelheim, Roche, Bristol-Myers Squibb, Pfizer, Novartis, Celldex Therapeutics, Foundation Medicine, Eli Lilly, and the Foundation for Clinical and Applied Cancer Research (FICMAC). C.R. is a speaker for Merck Sharp and Dohme, AstraZeneca; has research collaborations with Guardant Health; advisory board activity: Archer, Inivata and MD Serono, Novartis, and BMS; non-financial support from Guardant Health; research grant from LCRF-Pfizer. A.R. reports an advisory role for AstraZeneca and MSD. U.M. received personal fees (as a consultant and/or speaker bureau) from Boehringer Ingelheim, Roche, MSD, Amgen, Thermo Fisher Scientifics, Diaceutics, GSK, Merck, and AstraZeneca, unrelated to the current work. The other authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Signaling pathways recurrent affected in small cell lung cancer (SCLC) and frequently aberrant genes (created with BioRender.com, accessed on 28 March 2021).
Figure 2
Figure 2
ASCL1 overexpression in SCLC and exploitation of DLL3 as therapeutic target (created with BioRender.com, accessed on 24 February 2021).
See this image and copyright information in PMC

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