Institut de recherches cliniques de Montréal (IRCM)
Domaine : Cancer
Tumor recurrence is a common and often lethal consequence of cancer. The targeted anticancer strategies that were developed in the past few years often achieve prolonged cancer remission, but in many cases fail to achieve a cure. Therefore, additional medications are needed to prevent tumor relapse. Research using animal models suggests that potential for recurrence is influenced by multiple factors, including genetic mutations present in the tumor prior to treatment. The presence of oncogenic mutations is the main characteristic of tumor cells that distinguishes them from the normal cells. These oncogenic mutations can be inhibited by targeted anti-cancer therapies. Dramatic responses to a handful of new drugs that are given to patients with a specific mutation in their tumors, provide hope and relief to patients and their families. But the emerging pattern is that although these drugs can shrink solid tumors and extend patients' lives, they never completely eliminate the cancer. While multiple sequential oncogenic mutations cooperate in the malignant transformation of mammalian cells, but only single mutant proteins have been targeted so far. The goal of our proposal is determine whether inactivation of multiple oncogenes may produce longer remissions or even a cure. To do so, we have developed animal models that faithfully recapitulate key features of human breast cancer progression, including drug resistance and recurrence. Our animal models allow us to mimic highly effective targeted therapies to evaluate tumor regression in vivo and cancer cell death in vitro, and to address the following specific questions: Which kind of drug is better for women diagnosed with breast cancer harboring amplification of MYC and PI3K/PTEN pathway dysregulation? Should the drugs be used in combination or are they more effective when given as single agents?