Clinical insights into small cell lung cancer: Tumor heterogeneity, diagnosis, therapy, and future directions

Abstract

Small cell lung cancer (SCLC) is characterized by rapid growth and high metastatic capacity. It has strong epidemiologic and biologic links to tobacco carcinogens. Although the majority of SCLCs exhibit neuroendocrine features, an important subset of tumors lacks these properties. Genomic profiling of SCLC reveals genetic instability, almost universal inactivation of the tumor suppressor genes TP53 and RB1, and a high mutation burden. Because of early metastasis, only a small fraction of patients are amenable to curative‐intent lung resection, and these individuals require adjuvant platinum‐etoposide chemotherapy. Therefore, the vast majority of patients are currently being treated with chemoradiation with or without immunotherapy. In patients with disease confined to the chest, standard therapy includes thoracic radiotherapy and concurrent platinum‐etoposide chemotherapy. Patients with metastatic (extensive‐stage) disease are treated with a combination of platinum‐etoposide chemotherapy plus immunotherapy with an anti‐programmed death‐ligand 1 monoclonal antibody. Although SCLC is initially very responsive to platinum‐based chemotherapy, these responses are transient because of the development of drug resistance. In recent years, the authors have witnessed an accelerating pace of biologic insights into the disease, leading to the redefinition of the SCLC classification scheme. This emerging knowledge of SCLC molecular subtypes has the potential to define unique therapeutic vulnerabilities. Synthesizing these new discoveries with the current knowledge of SCLC biology and clinical management may lead to unprecedented advances in SCLC patient care. Here, the authors present an overview of multimodal clinical approaches in SCLC, with a special focus on illuminating how recent advancements in SCLC research could accelerate clinical development.

m 6 A demethylase ALKBH5 regulates TP53 to promote malignant transformation of lung cells induced by radon exposure via BTG2-mediated mitochondrial pathway

“…The evidence within the context of pulmonary oncology appears to exhibit a degree of contradiction, which may suggest a dependency on the speci c subtype of lung carcinoma. The speci city of lung cancer subtypes may in uence the pathobiological characteristics and clinical manifestations of the disease, resulting in a heterogeneous response to uniform therapeutic strategies across different subtypes [51]. Here, we found global m 6 A methylation level was increased, while ALKBH5 was downregulated in radon-exposed lung cells.…”

Clinical and Genetic Analysis of Li-Fraumeni Syndrome with Novel TP53 Mutations

“…Yang et al [29] demonstrated increased sensitivity of triple-negative breast cancer to PD-1 immunotherapy by restoring the activity of p53 protein carrying TP53 mutations. Megyesfalvi Z et al [30] found widespread inactivation of the TP53 gene in small cell lung cancer, suggesting potential e cacy of immunotherapy in this context. Chen et al [31] reported the rst case of CAR-T cell therapy in an LFS patient with hematological malignancy, suggesting that CAR-T cell therapy may be an alternative option compared to traditional chemotherapy and allogeneic hematopoietic stem cell transplantation.…”

Jaundice and Higher Procalcitonin Level Revealing a Small-Cell Lung Cancer With Pancreatic Metastasis: A Case Report From Eastern Morocco

“…As well as this dilemma is avoided by completing a whole immunochemistry panel. The most needed in practice are neuroendocrine markers, such as chromogranin, synaptophysin, and CD56; another new neuroendocrine marker is INSM1 [11].…”