Format

Send to

Choose Destination
See comment in PubMed Commons below
Expert Opin Ther Targets. 2013 May;17(5):507-31. doi: 10.1517/14728222.2013.764990. Epub 2013 Jan 30.

Targeting the RAS oncogene.

Author information

  • 1Boston University School of Medicine, Cancer Research Center , 72 E. Concord St. Boston MA, 02118 , USA.

Abstract

INTRODUCTION:

The Ras proteins (K-Ras, N-Ras, and H-Ras) are GTPases that function as molecular switches for a variety of critical cellular activities and their function is tightly and temporally regulated in normal cells. Oncogenic mutations in the RAS genes, which create constitutively-active Ras proteins, can result in uncontrolled proliferation or survival in tumor cells.

AREAS COVERED:

The paper discusses three therapeutic approaches targeting the Ras pathway in cancer: i) Ras itself, ii) Ras downstream pathways, and iii) synthetic lethality. The most adopted approach is targeting Ras downstream signaling, and specifically the PI3K-AKT-mTOR and Raf-MEK pathways, as they are frequently major oncogenic drivers in cancers with high Ras signaling. Although direct targeting of Ras has not been successful clinically, newer approaches being investigated in preclinical studies, such as RNA interference-based and synthetic lethal approaches, promise great potential for clinical application.

EXPERT OPINION:

The challenges of current and emerging therapeutics include the lack of "tumor specificity" and their limitation to those cancers which are "dependent" on aberrant Ras signaling for survival. While the newer approaches have the potential to overcome these limitations, they also highlight the importance of robust preclinical studies and bidirectional translational research for successful clinical development of Ras-related targeted therapies.

[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Taylor & Francis Icon for PubMed Central
    Loading ...
    Write to the Help Desk