Landscape and Treatment Options of Shapeshifting Small Cell Lung Cancer

• Published in: Journal of clinical medicine Vol. 13; no. 11; p. 3120
• Main Authors: Gu, Yijun, Benavente, Claudia A
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 26.05.2024; MDPI
• Subjects: Cancer; Cancer therapies; Cell cycle; Cell differentiation; Cell growth; Chemotherapy; DNA binding proteins; Epigenetics; Genes; Genomes; Growth factors; Health aspects; immunotherapy; Kinases; Lung cancer; Lung cancer, Small cell; Medical prognosis; Metastasis; Mutation; Review; small cell lung cancer; Smoking; targeted therapy; Tobacco; Transcription factors; tumor plasticity; Tumors; targeted therapy; small cell lung cancer; immunotherapy; tumor plasticity
• ISSN: 2077-0383; 2077-0383
• DOI: 10.3390/jcm13113120

Small cell lung cancer (SCLC) is a deadly neuroendocrine malignancy, notorious for its rapid tumor growth, early metastasis, and relatively "cold" immune environment. Only standard chemotherapies and a few immune checkpoint inhibitors have been approved for SCLC treatment, revealing an urgent need for novel therapeutic approaches. Moreover, SCLC has been recently recognized as a malignancy with high intratumoral and intertumoral heterogeneity, which explains the modest response rate in some patients and the early relapse. Molecular subtypes defined by the expression of lineage-specific transcription factors (ASCL1, NEUROD1, POU2F3, and, in some studies, YAP1) or immune-related genes display different degrees of neuroendocrine differentiation, immune cell infiltration, and response to treatment. Despite the complexity of this malignancy, a few biomarkers and targets have been identified and many promising drugs are currently undergoing clinical trials. In this review, we integrate the current progress on the genomic landscape of this shapeshifting malignancy, the characteristics and treatment vulnerabilities of each subtype, and promising drugs in clinical phases.