Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Clin Cancer Res. 2010 Mar 1;16(5):1373-83. doi: 10.1158/1078-0432.CCR-09-1218. Epub 2010 Feb 23.

HER3 comes of age: new insights into its functions and role in signaling, tumor biology, and cancer therapy.

Author information

  • 1Department of Medicine & Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California 94143-1387, USA.

Abstract

The human epidermal growth family (HER) of tyrosine kinase receptors underlies the pathogenesis of many types of human cancer. The oncogenic functions of three of the HER proteins can be unleashed through amplification, overexpression, or mutational activation. This has formed the basis for the development of clinically active targeted therapies. However, the third member HER3 is catalytically inactive, not found to be mutated or amplified in cancers, and its role and functions have remained shrouded in mystery. Recent evidence derived primarily from experimental models now seems to implicate HER3 in the pathogenesis of several types of cancer. Furthermore, the failure to recognize the central role of HER3 seems to underlie resistance to epidermal growth factor receptor (EGFR)- or HER2-targeted therapies in some cancers. Structural and biochemical studies have now greatly enhanced our understanding of signaling in the HER family and revealed the previously unrecognized activating functions embodied in the catalytically impaired kinase domain of HER3. This renewed interest and mechanistic basis has fueled the development of new classes of HER3-targeting agents for cancer therapy. However, identifying HER3-dependent tumors presents a formidable challenge and the success of HER3-targeting approaches depends entirely on the development and power of predictive tools.

PMID:
20179223
[PubMed - indexed for MEDLINE]
PMCID:
PMC2831167
Free PMC Article

Images from this publication.See all images (3)Free text

Figure 1a
Figure 1b
Figure 1c
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk