First-line treatments for KRAS-mutant non-small cell lung cancer: current state and future perspectives

Cancer Biol Ther. 2025 Dec;26(1):2441499. doi: 10.1080/15384047.2024.2441499. Epub 2024 Dec 16.

Abstract

KRAS mutations are common in non-small cell lung cancer (NSCLC) and are associated with patient prognosis; however, targeting KRAS has faced various difficulties. Currently, immunotherapy, chemotherapy, and chemoimmunotherapy play pivotal roles in the first-line treatment of KRAS-mutated NSCLC. Here, we summarize the current evidence on first-line therapies and compare the treatment outcomes and biomarkers for different regimens. KRAS inhibitors and other emerging alternative treatments are also discussed, as combining these drugs with immunotherapy may serve as a promising first-line treatment for KRAS-mutated NSCLC in the future. We hope that this review will assist in first-line treatment choices and shed light on the development of novel agents for KRAS-mutated NSCLC.

Keywords: Kirsten rat sarcoma viral oncogene (KRAS); anti-vascular therapy; chemotherapy; first-line; immune checkpoint inhibitors (ICIs).

Publication types

  • Review

MeSH terms

  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Carcinoma, Non-Small-Cell Lung* / therapy
  • Humans
  • Immunotherapy / methods
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / pathology
  • Lung Neoplasms* / therapy
  • Molecular Targeted Therapy / methods
  • Mutation*
  • Proto-Oncogene Proteins p21(ras)* / genetics

Substances

  • Proto-Oncogene Proteins p21(ras)
  • KRAS protein, human

Grants and funding

The study is supported by the National High Level Hospital Clinical Research Funding (2022-PUMCH-C-054).