Development of inhibitors for CUX1 and PARG, two novel therapeutic targets for hard-to-treat breast cancers

Challenge: Triple-negative breast cancer (TNBC) accounts for 15 to 20 % of all breast cancer patients, but for about 25 % of all breast cancer deaths. There is currently no targeted treatment for TNBC, while only about 30 % of TNBCs are sensitive to conventional therapies. In addition, no more than 50 % of HER2-positive (HER2+) breast cancer patients respond to targeted therapy. Patients are currently treated using conventional therapies, but remission is usually short and relapses frequently. There is, therefore, an urgent need for new therapies for these types of breast cancer.

Solution: The research team has identified and validated two novel and “druggable” therapeutic targets, namely CUX1 and PARG, that are important key regulators of DNA repair mechanisms. This project in collaboration with the NEOMED Institute aims to identify new CUX1 and PARG inhibitors using a medicinal chemistry approach which combines high-throughput screening, validation assays, reiterative rounds of structure-activity relationship (SAR) studies, pharmacokinetic profiling, and toxicity assessment either towards breast normal cells or breast tumor cells. CUX1 and PARG biomarkers are also developed in parallel for patient stratification and target engagement.

Expected Achievements/Impact: The resulting lead compounds are expected to become drug candidates around which NEOMED will then be able to create spin-off companies to advance drugs into clinical trials to ultimately become the medicines of tomorrow for the benefit of patients. The development of biomarkers for patient stratification will further benefit industrial partners on the cost, feasibility, and effectiveness of the clinical development of these new drugs and allow for personalized medicine thus bringing new hope for patients with hard-to-treat TNBCs.













Principal Investigator:

Alain Nepveu
McGill University


Michael Witcher
Jewish General Hospital

Kemal Payza
NEOMED Institute

Ongoing Project
$ 1,368,000 / 3 years
Supported by CQDM through:

And by co-funding partners:
• Canadian Cancer Society (CCS)
• NEOMED Institute