KRAS: A Promising Therapeutic Target for Cancer Treatment

Curr Top Med Chem. 2019;19(23):2081-2097. doi: 10.2174/1568026619666190905164144.

Abstract

Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) is the most commonly mutated oncogene in human cancer. The developments of many cancers depend on sustained expression and signaling of KRAS, which makes KRAS a high-priority therapeutic target. Scientists have not successfully developed drugs that target KRAS, although efforts have been made last three decades. In this review, we highlight the emerging experimental strategies of impairing KRAS membrane localization and the direct targeting of KRAS. We also conclude the combinatorial therapies and RNA interference technology for the treatment of KRAS mutant cancers. Moreover, the virtual screening approach to discover novel KRAS inhibitors and synthetic lethality interactors of KRAS are discussed in detail.

Keywords: Cancer treatment; KRAS; Mutant cancers; Oncogene; Therapeutic target; Viral oncogene..

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Humans
  • Mutation
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Oncogene Protein p21(ras) / antagonists & inhibitors*
  • Oncogene Protein p21(ras) / genetics
  • Oncogene Protein p21(ras) / metabolism
  • Proto-Oncogene Proteins p21(ras) / antagonists & inhibitors*
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Proto-Oncogene Proteins p21(ras) / metabolism*
  • RNA Interference

Substances

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