Small cells – big issues: biological implications and preclinical advancements in small cell lung cancer

Solta, Anna and Ernhofer, Büsra and Boettiger, Kristiina and Megyesfalvi, Zsolt and Heeke, Simon and Hoda, Mir Alireza and Lang, Christian and Aigner, Clemens and Hirsch, Fred R. and Schelch, Karin and Döme, Balazs (2024) Small cells – big issues: biological implications and preclinical advancements in small cell lung cancer. MOLECULAR CANCER, 23 (1). No.-41. ISSN 1476-4598

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Abstract

Current treatment guidelines refer to small cell lung cancer (SCLC), one of the deadliest human malignancies, as a homogeneous disease. Accordingly, SCLC therapy comprises chemoradiation with or without immunotherapy. Meanwhile, recent studies have made signifcant advances in subclassifying SCLC based on the elevated expression of the transcription factors ASCL1, NEUROD1, and POU2F3, as well as on certain infammatory characteristics. The role of the transcription regulator YAP1 in defning a unique SCLC subset remains to be established. Although preclinical analyses have described numerous subtype-specifc characteristics and vulnerabilities, the so far non-existing clinical subtype distinction may be a contributor to negative clinical trial outcomes. This comprehensive review aims to provide a framework for the development of novel personalized therapeutic approaches by compiling the most recent discoveries achieved by preclinical SCLC research. We highlight the challenges faced due to limited access to patient material as well as the advances accomplished by implementing state-of-the-art models and methodologies.

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