[Therapeutic possibilities in KRAS-mutant lung adenocarcinoma]

Magy Onkol. 2020 Sep 23;64(3):231-244. Epub 2020 Aug 6.
[Article in Hungarian]

Abstract

KRAS mutations are the most common gain-of-function alterations in lung adenocarcinoma (LADC) in the western countries. Although the different mutations of the KRAS gene have been identified decades ago, the development of drugs targeting the KRAS protein directly have not been successful due to the lack of small molecule binding sites and the extremely high affinity to cellular GTP. Indirect strategies to inhibit KRAS (e.g. inhibitors of farnesyltransferase, prenylation, synthetic lethal partners and KRAS downstream signaling) have so far also failed. In recent times, however several compounds have been developed that target subtype- specific KRAS mutations. Covalent KRAS G12C-specific inhibitors showed the most promising preclinical results. Below, we summarize the predictive and prognostic value of KRAS mutations in LADC as well as the current targeting strategies.

Publication types

  • Review

MeSH terms

  • Adenocarcinoma of Lung / drug therapy*
  • Adenocarcinoma of Lung / genetics*
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics*
  • Mutation*
  • Prognosis
  • Proto-Oncogene Proteins p21(ras) / genetics*

Substances

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