Cancer targets in the Ras pathway

Cold Spring Harb Symp Quant Biol. 2005;70:461-7. doi: 10.1101/sqb.2005.70.044.

Abstract

Ras proteins play a direct causal role in human cancer and in other diseases. Mutant H-Ras, N-Ras, and K-Ras occur in varying frequencies in different tumor types, for reasons that are not known. Other members of the Ras superfamily may also contribute to cancer. Mutations also occur in downstream pathways, notably B-Raf, PTEN, and PI 3' kinase: These pathways interact at multiple points, including cyclin D1, and act synergistically. In some cases mutations in Ras and effectors are mutually exclusive; in other cases, they coexist. Drugs blocking elements of the pathway are in different stages of clinical development. One of these, the Raf kinase/VEGF-R2 inhibitor Sorafenib, has already been approved for treatment of renal cancer and is being tested in other indications. However, therapeutic targets in the Ras pathway have not yet been fully validated as bona fide targets.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / therapeutic use
  • Benzenesulfonates / chemistry
  • Benzenesulfonates / therapeutic use
  • Drug Design
  • Female
  • Genes, ras*
  • Humans
  • Male
  • Models, Biological
  • Mutation
  • Neoplasms / drug therapy*
  • Neoplasms / genetics*
  • Neoplasms / physiopathology
  • Niacinamide / analogs & derivatives
  • Phenylurea Compounds
  • Pyridines / chemistry
  • Pyridines / therapeutic use
  • Signal Transduction / drug effects
  • Sorafenib
  • ras Proteins / antagonists & inhibitors*
  • ras Proteins / physiology

Substances

  • Antineoplastic Agents
  • Benzenesulfonates
  • Phenylurea Compounds
  • Pyridines
  • Niacinamide
  • Sorafenib
  • ras Proteins