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Author correction: Molecular subtypes of small cell lung cancer: a synthesis of human and mouse model dataRudin, CM; Poirier, JT; Byers, LA; Dive, Caroline; Dowlati, A; George, J; Heymach, JV; Johnson, JE; Lehman, JM; MacPherson, D; et al. (2019)An amendment to this paper has been published and can be accessed via a link at the top of the paper. Erratum for Molecular subtypes of small cell lung cancer: a synthesis of human and mouse model data. [Nat Rev Cancer. 2019]
Molecular subtypes of small cell lung cancer: a synthesis of human and mouse model dataRudin, CM; Poirier, JT; Byers, LA; Dive, Caroline; Dowlati, A; George, J; Heymach, JV; Johnson, JE; Lehman, JM; MacPherson, D; et al. (2019)Small cell lung cancer (SCLC) is an exceptionally lethal malignancy for which more effective therapies are urgently needed. Several lines of evidence, from SCLC primary human tumours, patient-derived xenografts, cancer cell lines and genetically engineered mouse models, appear to be converging on a new model of SCLC subtypes defined by differential expression of four key transcription regulators: achaete-scute homologue 1 (ASCL1; also known as ASH1), neurogenic differentiation factor 1 (NeuroD1), yes-associated protein 1 (YAP1) and POU class 2 homeobox 3 (POU2F3). In this Perspectives article, we review and synthesize these recent lines of evidence and propose a working nomenclature for SCLC subtypes defined by relative expression of these four factors. Defining the unique therapeutic vulnerabilities of these subtypes of SCLC should help to focus and accelerate therapeutic research, leading to rationally targeted approaches that may ultimately improve clinical outcomes for patients with this disease.
New approaches to small cell lung cancer therapy : from the laboratory to the clinicPoirier, JT; George, J; Owonikoko, TK; Berns, A; Brambilla, E; Byers, LA; Carbone, D; Chen, HJ; Christensen, CL; Dive, Caroline; et al. (2020)Small cell lung cancer patient outcomes have not yet been significantly impacted by the revolution in precision oncology, primarily due to a paucity of genetic alterations in actionable driver oncogenes. Nevertheless, systemic therapies that include immunotherapy are beginning to show promise in the clinic. While these results are encouraging, many patients do not respond to or rapidly recur after current regimens, necessitating alternative or complementary therapeutic strategies. In this review, we discuss ongoing investigations into the pathobiology of this recalcitrant cancer and the therapeutic vulnerabilities that are exposed by the disease state. Included within this discussion is a snapshot of the current biomarker and clinical trial landscapes for small cell lung cancer. Finally, we identify key knowledge gaps that should be addressed in order to advance the field in pursuit of reduced small cell lung cancer mortality. This review largely summarizes work presented at the Third Biennial IASLC Small Cell Lung Cancer Meeting.