Transitioning to a Personalized Approach in Molecularly Subtyped Small-Cell Lung Cancer (SCLC)

Int J Mol Sci. 2024 Apr 10;25(8):4208. doi: 10.3390/ijms25084208.

Abstract

Lung cancer has become a major public health concern, standing as the leading cause of cancer-related deaths worldwide. Among its subtypes, small-cell lung cancer (SCLC) is characterized by aggressive and rapid growth, poor differentiation, and neuroendocrine features. Typically, SCLC is diagnosed at an advanced stage (extensive disease, ED-SCLC), with distant metastases, and is strongly associated with tobacco smoking and has a poor prognosis. Recent clinical trials, such as CASPIAN and IMpower133, have demonstrated promising outcomes with the incorporation of immune checkpoint inhibitors in first-line chemotherapy, leading to prolonged progression-free survival and overall survival in patients with ED-SCLC compared to standard chemotherapy. Other studies have emphasized the potential for future development of molecularly targeted therapies in SCLC patients, including inhibitors of IGF-1R, DLL3, BCL-2, MYC, or PARP. The molecular subdivision of SCLC based on transcriptomic and immunohistochemical analyses represents a significant advancement in both diagnostic and clinical approaches in SCLC patients. Specific molecular pathways are activated within distinct transcriptome subtypes of SCLC, offering the potential for personalized treatment strategies, such as targeted therapies and immunotherapies. Such tailored approaches hold promise for significantly improving outcomes in SCLC patients.

Keywords: immunotherapy; molecular types; molecularly targeted therapies; small-cell lung cancer; transcriptome pattern.

Publication types

  • Review

MeSH terms

  • Biomarkers, Tumor / metabolism
  • Humans
  • Immunotherapy / methods
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / metabolism
  • Lung Neoplasms* / pathology
  • Lung Neoplasms* / therapy
  • Molecular Targeted Therapy
  • Precision Medicine* / methods
  • Small Cell Lung Carcinoma* / genetics
  • Small Cell Lung Carcinoma* / metabolism
  • Small Cell Lung Carcinoma* / pathology
  • Small Cell Lung Carcinoma* / therapy

Substances

  • Biomarkers, Tumor

Grants and funding

This research received no external funding.