The AACR-Genentech BioOncology Fellowship for Cancer Research on the HER Family Pathway provides funding to postdoctoral and clinical research fellows working at an academic, medical or research institution who will be in the first, second or third year of their postdoctoral training at the start of the grant term. Proposed research projects must have direct applicability to the HER family pathway (basic, clinical, translational or epidemiological cancer research).
2009 GRANTEE
Marcia Campbell, Ph.D.
Postdoctoral Fellow, University of California, San Francisco, CA
Towards a Druggable HER3; a Structure, Function and Signaling Analysis
"Approximately 25 percent of breast cancers are characterized by amplification of the Human Epidermal Growth Factor Receptor-2 (HER2) gene and two decades of evidence strongly implicates HER2 in the pathogenesis of this disease. This identifies HER2 as an Achilles' heel and suggests that drugs that can be designed to inactivate HER2 would be highly effective and may eradicate this disease.
"However, scientific progress in recent years shows that HER2 does not function alone, rather it functions cooperatively with its equally important partner HER3 and it is the HER2-HER3 dimer that drives this disease. The current drugs are only weakly able to inhibit the HER2-HER3 dimer and advances in understanding how the HER2-HER3 dimer functions should allow the development of a new generation of effective drugs.
"Based on the most recent scientific evidence, we have developed hypotheses regarding how the HER2-HER3 dimer can be inactivated. We think there is a particular conformation of HER3 that is most important, yet has been overlooked. We also think the kinase domain of HER3, which has previously been thought to be unimportant, is actually critically important in the HER2-HER3 complex. We are going to test these hypotheses using mutant forms of HER3 that will allow us to identify which conformations are important as well as study the kinase domain to identify regions critical to HER2-amplified tumorigenesis. These data will be used in future research to assist us in developing a prototype antibody drug to test whether the HER2-HER3 complex can be effectively disrupted by this type of drug.
"It is an honor to be receiving the AACR-Genentech BioOncology Fellowship for Cancer Research on the HER Family Pathway. This award will allow me to carry out research in the field of HER family signaling in breast cancer that promises to provide important insights into breast cancer while at the same time allowing me to develop as a scientist and acquire the skills necessary to make important advances in the field. I am extremely grateful to my previous supervisor, Dr. Susan Andrew, and my current supervisor, Dr. Mark Moasser, for their continuous support and mentorship that has been critical in my development as a scientist."
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