New weapons to penetrate the armor: Novel reagents and assays developed at the NCI RAS Initiative to enable discovery of RAS therapeutics

Semin Cancer Biol. 2019 Feb:54:174-182. doi: 10.1016/j.semcancer.2018.02.006. Epub 2018 Feb 9.

Abstract

Development of therapeutic strategies against RAS-driven cancers has been challenging due in part to a lack of understanding of the biology of the system and the ability to design appropriate assays and reagents for targeted drug discovery efforts. Recent developments in the field have opened up new avenues for exploration both through advances in the number and quality of reagents as well as the introduction of novel biochemical and cell-based assay technologies which can be used for high-throughput screening of compound libraries. The reagents and assays developed at the NCI RAS Initiative offer a suite of new weapons that could potentially be used to enable the next generation of RAS drug discovery efforts with the hope of finding novel therapeutics for a target once deemed undruggable.

Keywords: Assay development; Biochemical assays; Cell-based assays; Drug discovery; RAS.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Drug Discovery* / methods
  • Drug Discovery* / standards
  • Drug Screening Assays, Antitumor / methods
  • Drug Screening Assays, Antitumor / standards
  • Gene Expression Regulation, Neoplastic / drug effects
  • High-Throughput Screening Assays
  • Humans
  • Mutation
  • Neoplasms / drug therapy
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Protein Binding / drug effects
  • Quality Control
  • Signal Transduction / drug effects
  • ras Proteins / antagonists & inhibitors*
  • ras Proteins / genetics
  • ras Proteins / metabolism

Substances

  • Antineoplastic Agents
  • ras Proteins