KRAS as a Therapeutic Target

Abstract

KRAS proteins play a major role in human cancer, but have not yielded to therapeutic attack. New technologies in drug discovery and insights into signaling pathways that KRAS controls have promoted renewed efforts to develop therapies through direct targeting of KRAS itself, new ways of blocking KRAS processing, or by identifying targets that KRAS cancers depend on for survival. Although drugs that block the well-established downstream pathways, RAF-MAPK and PI3K, are being tested in the clinic, new efforts are under way to exploit previously unrecognized vulnerabilities, such as altered metabolic networks, or novel pathways identified through synthetic lethal screens. Furthermore, new ways of suppressing KRAS gene expression and of harnessing the immune system offer further hope that new ways of treating KRAS are finally coming into view. These issues are discussed in this edition of CCR Focus.

Conflict of interest statement

Disclosure of Potential Conflicts of Interest: No potential conflicts of interest were disclosed.

©2015 American Association for Cancer Research.

Figures

Figure 1

The Ras pathway. RAS proteins are activated by GEFs (guanine nucleotide exchange factors), boxed in green, and inactivated by GAPs (GTPase activating proteins), boxed in red. Protein names correcond to gene names from TCGA (see ref 8. for conversion to protein names). Pathways downstream of Ras include RASSF proteins, RalGDS, the Raf kinases, and PI 3 kinases.