Grant: Project Grant

Metastatic cancers are the most aggressive cancers, accounting for 90% of all cancer-related deaths. Radiation as well as chemotherapy are not effective enough to fight against these types of cancers. It is now clearly established that there is a link between cancer stem cells (CSCs) and the development of metastases. CSCs represent a small reservoir of cells within the tumor that are responsible for the development of metastases and resistance to standard treatments. By specifically targeting cancer stem cells, we could prevent the formation of metastases, resistance to standard therapies but also cancer recurrences. It is therefore essential to find new efficient therapies that allow us to eradicate CSCs that are not targeted by current chemotherapy. We have started to study triple-negative breast cancers (TNBCs), which are the most aggressive and the deadliest of the 4 subtypes of breast cancers. Patients with TNBCs have limited treatment options and their life-threatening condition is most often clinically unfavorable. TNBC develops and spreads faster than other breast cancers. Most of the time, detection of these tumors is performed too late, and the cancer is detected at later stages, where cancer cells have already begun to metastasize by migrating rapidly from the tumor to neighboring organs; especially to the lungs, bones and the brain. The goal of this project is to develop an effective "targeted therapy" in this type of breast cancer. Our team has recently demonstrated a regulatory pathway in the development of cancer stem cells: the cyclin-4-dependent kinase (CDK4). We found that blocking the biological action of this protein, CDK4, prevents self-renewal of CSCs and eliminates normal and chemotherapy-resistant cancer cells in the TNBC. This project proposes to develop new small molecules capable of inhibiting a fundamental biological pathway (CDK4) used by CSCs in TNBCs