Research

QBCF Strategic Grants Program

Research Factsheet 

PROFESSOR JAMES L. GLEASON

McGILL UNIVERSITY, MONTRÉAL

PROJECT TITLE : Hybrid antiestrogen/histone deacetylase inhibitors as new breast cancer therapies

PRINCIPAL INVESTIGATOR Prof. James L. Gleason

INSTITUTE McGill University, Montréal

CO-APPLICANTProf. Sylvie Mader, Montréal University, Montréal

Total Research Budget: $450 000

Non-Scientific Summary*:

One of the mainline adjuvant treatments of all stages of estrogen receptor positive breast cancer is administration of estrogen receptor (ER) antagonists, the most common of which is tamoxifen.

ER antagonists are used in breast cancer treatment to prevent tumor recurrence. In addition, ER antagonists can be used to reduce the incidence of breast cancer in those women identified as high-risk individuals (e.g. family history of breast cancer). While ER antagonist treatment can significantly reduce tumor formation and/or recurrence, it is not effective in all cases. For instance, a comprehensive study showed that mortality rates in women with early stage breast cancers after 5 years of treatment with tamoxifen are still on the order of 25%. Furthermore, tamoxifen has several side-effects, the most significant of which is an increase in occurrence of endometrial cancer.

Thus, there is a continued need to improve on known ER antagonists. Histone deacetylase inhibitors are a new class of compounds being investigated by many groups as potential anticancer agents. Recent findings from our labs and others have shown that co-treatment with an ER antagonist and an inhibitor of histone deacetylase can significantly decrease the growth of breast cancer cells.

Importantly, this type of treatment is effective in cancer cells that are resistant to ER antagonist therapy alone. Our research will develop an entirely new class of anticancer compounds. Our goal is to develop a single drug that acts as both an ER antagonist and a histone deacetylase inhibitor. It is expected that this combination drug will prove more effective than separate treatment with two drugs, as linking histone deacetylase inhibitory activity to estrogen derivatives can help to localize this activity in estrogen receptor expressing breast cancer cells. This may allow to use lower drug concentrations, reducing side effects.