The research interests of Matthew M. Ames, Ph.D., focus on the study and evaluation of novel anti-cancer agents, with an emphasis on those with novel molecular targets and the role of genetic variation (pharmacogenetics) in how patients individually respond to drug-based cancer therapies.
- Tamoxifen pharmacogenetics. A current example of Dr. Ames' research involves defining the role of genetic variation in the risk of cancer recurrence in women with estrogen receptor positive breast cancer treated with the hormonal agent tamoxifen. Dr. Ames, in collaboration with Matthew P. Goetz, M.D., has found that the presence of certain variant alleles of the cytochrome P450 2D6 gene (associated with metabolism of tamoxifen to the active metabolite endoxifen) is highly correlated with the risk of recurrence.
- Endoxifen drug development. Drs. Goetz and Ames have been extensively involved in the development of the active tamoxifen metabolite (endoxifen) as a new therapy for the treatment of estrogen receptor positive breast cancer. Early clinical trials are very promising and suggest a role for endoxifen not only in the treatment of "upfront" estrogen receptor positive breast cancer (thus bypassing the genetic issues with tamoxifen) but also in the treatment of women who have failed other hormonal therapies for their disease. Further, mechanism of action studies are consistent with a novel mechanism of action for endoxifen, in addition to the activity associated with a more active form of tamoxifen.
Significance to patient care
Dr. Ames' studies with tamoxifen, and especially endoxifen, will hopefully lead to a new, effective therapy for the treatment of estrogen receptor positive breast cancer.