Targeting the "undruggable" RAS with biologics

Adv Cancer Res. 2022:153:237-266. doi: 10.1016/bs.acr.2021.07.006. Epub 2021 Aug 13.

Abstract

RAS proteins represent critical drivers of tumor development and thus are the focus of intense efforts to pharmacologically inhibit these proteins in human cancer. Although recent success has been attained in developing clinically efficacious inhibitors to KRASG12C, there remains a critical need for developing approaches to inhibit additional mutant RAS proteins. A number of anti-RAS biologics have been developed which reveal novel and potentially therapeutically targetable vulnerabilities in oncogenic RAS. This review will discuss the growing field of anti-RAS biologics and potential development of these reagents into new anti-RAS therapies.

Keywords: Antibodies; Cyclic peptides; DARPins; Intrabodies; Miniproteins; Monobodies; PROTACs; Sso7d; Stapled peptides; Toxin peptidases; cancer therapeutics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Biological Products* / pharmacology
  • Biological Products* / therapeutic use
  • Humans
  • Mutation
  • Neoplasms* / pathology
  • ras Proteins / metabolism

Substances

  • Biological Products
  • ras Proteins