Grant: Project Grant

Metastatic cancer is a largely incurable disease and responsible for 90% of human cancer-related deaths. Cancer stem cells can drive not only tumor initiation, but also metastasis in various human cancer types. This distinct subpopulation of cancer cells utilize their self-renewal ability to generate and persistently propagate a heterogeneous tumor resulting in cancer relapse. Remarkably, this cell population also displays resistance to radiation and chemotherapy based treatments, resulting in tumor relapse, ultimately causing cancer patient death. Therefore, targeting cancer stem cells is a priority for the development of novel therapies. We found the enzyme COX-2 to be highly expressed in aggressive breast cancer and showed that it propagates and increases cancer stem cell numbers, further leading to tumor metastasis and resistance to chemotherapy. This proposal is to address the molecular mechanisms by which COX-2 regulates cancer stem cell generation/behavior and offer potential anti-cancer therapies for patients with metastatic and chemotherapy-resistant TNBCs.