Impact épigénétique de la dérégulation de la Poly (ADP) ribosylation dans le cancer du sein


Michael Witcher

Institut Lady Davis de recherches médicales de l'Hôpital général juif


Domaine : cancer

Concours 2013-2014


Fondation du cancer du sein du Québec

Cancer is characterized by abnormal, uncontrolled division of cells. Recent evidence has shown that one of the initiating steps leading to this type of malignant growth in breast cancer is the silencing (switching off) of tumor suppressor genes. These genes typically control cell growth to ensure that proliferation does not exceed normal limitations, but once these genes are turned off, cancer can arise. Turning these genes back on is a relevant therapeutic goal and several drugs that reactivate tumor suppressor genes have been tested in clinical trials.

However, the rational development of these types of drugs has been hampered by our lack of understanding as to why these tumor suppressor genes become silenced in the first place. My previous work uncovered a mechanism whereby tumor suppressors become silenced in breast cancer cells due to the dysfunction of an important regulatory protein.

Recently I discovered that this dysfunction is due to elevated levels and heightened activity of a protein called PARG in breast cancer cells. My current work suggests that inhibitors of PARG may be useful new therapeutic agents for breast cancer. Therefore, my current research efforts focus on understanding in more detail how PARG regulates tumor formation and exploring the potential of PARG inhibitors as novel therapeutic agents to fight breast cancer.