Precision medicine in non-small cell lung cancer: Current applications and future directions

Semin Cancer Biol. 2022 Sep:84:184-198. doi: 10.1016/j.semcancer.2020.07.009. Epub 2020 Jul 27.

Abstract

Advances in biomarkers, targeted therapies, and immuno-oncology have transformed the clinical management of patients with advanced NSCLC. For oncogene-driven tumors, there are highly effective targeted therapies against EGFR, ALK, ROS1, BRAF, TRK, RET, and MET. In addition, investigational therapies for KRAS, NRG1, and HER2 have shown promising results and may become standard-of-care in the near future. In parallel, immune-checkpoint therapy has emerged as an indispensable treatment modality, especially for patients lacking actionable oncogenic drivers. While PD-L1 expression has shown modest predictive utility, biomarkers for immune-checkpoint inhibition in NSCLC have remained elusive and represent an area of active investigation. Given the growing importance of biomarkers, optimal utilization of small tissue biopsies and alternative genotyping methods using circulating cell-free DNA have become increasingly integrated into clinical practice. In this review, we will summarize the current landscape and emerging trends in precision medicine for patients with advanced NSCLC with a special focus on predictive biomarker testing.

Keywords: Histological and molecular diagnostics; Liquid biopsy; Lung cancer diagnostics; Resistance to EGFR-TKIs; Tumor mutational burden.

Publication types

  • Review

MeSH terms

  • Biomarkers, Tumor / genetics
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / therapy
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / therapy
  • Mutation
  • Precision Medicine
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / therapeutic use
  • Proto-Oncogene Proteins

Substances

  • Biomarkers, Tumor
  • Proto-Oncogene Proteins
  • Protein-Tyrosine Kinases