Small Cell Lung Cancer Classification: Unraveling Heterogeneity to Enable Personalized Treatments
Small cell lung cancer (SCLC) is an aggressive thoracic disease characterized by rapid proliferation and early metastatic spread. The survival outcomes for patients with SCLC remain notoriously poor, underlining that only modest improvements have been achieved in clinical settings to date. However, insights gained from human tumors and preclinical models in recent years have shed light on the heterogeneous molecular profile of SCLC. Numerous research groups have, therefore, begun to stratify SCLC into subgroups based on differential transcription factor expression, the tumor immune microenvironment, and other criteria. As SCLC subtypes show major differences in their molecular landscape and biological behavior, they may offer unique therapeutic vulnerabilities and serve as a framework for future personalized clinical trials. Here, we summarize impactful classification attempts from the past 10 years, highlighting discrepancies and connections between the nomenclature of each study, and expound upon relevant factors of SCLC biology influencing subtype composition and plasticity. This review delves into the implications of subgrouping for understanding and treating SCLC, as well as potential future directions for SCLC research.
Authors
- Ildikó Kovács (ORCID: https://orcid.org/0000-0003-0742-8707)
- Abigail J. Deloria (ORCID: https://orcid.org/0000-0003-0380-4971)
- Ferenc Rényi-Vámos (ORCID: https://orcid.org/0000-0002-0555-2096)
- Karin Schelch (ORCID: https://orcid.org/0000-0001-8742-1737)
- Zsolt Megyesfalvi (ORCID: https://orcid.org/0000-0001-8552-6500)
- Christian Lang (ORCID: https://orcid.org/0000-0003-3779-4126)
- Balázs Döme (ORCID: https://orcid.org/0000-0001-8799-8624)
- Büsra Ernhofer (ORCID: https://orcid.org/0009-0008-2409-6402)
- Carl M. Gay (ORCID: https://orcid.org/0000-0002-4907-0718)
- Lauren A. Byers (ORCID: https://orcid.org/0000-0002-0780-2677)
- Fred R. Hirsch (ORCID: https://orcid.org/0000-0002-6885-1894)
- Julien Sage (ORCID: https://orcid.org/0000-0002-8928-9968)
- L. Horváth (ORCID: https://orcid.org/0009-0008-7646-756X)
- Clemens Aigner (ORCID: https://orcid.org/0000-0002-7787-991X)
- Kristiina Boettiger (ORCID: https://orcid.org/0009-0001-0602-5597)
- Evelyn Megyesfalvi (ORCID: https://orcid.org/0000-0002-1690-2450)
- Krisztina Bogos (ORCID: https://orcid.org/0009-0003-3719-0944)
- Maria Dorothea Pozonec (ORCID: https://orcid.org/0009-0000-3802-4946)
- Vivien Teglas (ORCID: https://orcid.org/0009-0003-5283-1658)
Institutions
- Semmelweis University (HU)
- Mount Sinai Health System (US)
- The University of Texas MD Anderson Cancer Center (US)
- Lund University (SE)
- Comprehensive Cancer Center Vienna (AT)
- National Institute of Oncology (HU)
- Stanford Medicine (US)
- Országos Korányi Tbc és Pulmonológiai Intézet (HU)
- University of Colorado Anschutz Medical Campus (US)
- Medical University of Vienna (AT)
- Stanford University (US)
- Icahn School of Medicine at Mount Sinai (US)
Publication Details
- Journal
- Cancer Research
- Published
- 2025-12-18
- DOI
- https://doi.org/10.1158/0008-5472.can-25-1483
- Primary Topic
- Lung Cancer Research Studies
- Type
- article
- Field-Weighted Citation Impact
- 0.00