KRAS as a druggable target in NSCLC: Rising like a phoenix after decades of development failures

Cancer Treat Rev. 2020 Apr;85:101978. doi: 10.1016/j.ctrv.2020.101978. Epub 2020 Feb 7.


Cancers of nearly all lineages harbor alterations that deregulate mitogen-activated protein kinase signaling, a crucial signaling pathway for tumor formation and maintenance. Of these, KRAS mutations are the most frequent gain-of-function alterations found in patients with cancer. In particular they represents the most common molecular alteration detected in non-small cell lung cancer (NSCLC) accounting for up to 25% of all oncogenic mutations. They were identified decades ago and prior efforts to target these proteins have been unsuccessful. KRAS mutation profiles (i.e. frequency of specific codon substitutions) in smokers and never-smokers are distinct and not all KRAS alterations are driver mutations. KRAS has evolved from a mutation with possible predictive value to a therapeutic target with great promise. Here, we will discuss the biology of KRAS in lung cancer and its clinical implications in oncology today and in the foreseeable future.

Keywords: Checkpoint inhibitors; KRAS; NSCLC.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Female
  • Forecasting
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Immunotherapy / methods
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality
  • Male
  • Molecular Targeted Therapy*
  • Mutation
  • Proto-Oncogene Proteins p21(ras) / drug effects
  • Proto-Oncogene Proteins p21(ras) / genetics*
  • Survival Analysis
  • Treatment Outcome


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