Grants - New York - Designated Grants - 2015

Jose Baselga, M.D., Ph.D. & Guotai Xu, Ph.D.

Funded in Collaboration With Stand Up To Cancer (SU2C)

The so called targeted therapies are effective in tumors that strictly depend on a given protein or cellular signaling (the target) for growth and survival. Hyperactivation of the PI3K pathway is frequent in breast cancers and its pharmacologic inhibition showed clinical responses. However, these molecules alone cannot elicit a durable inhibition of tumor growth because the tumor can adapt and compensate the inhibition of the pathway.

Thus, targeting these compensatory mechanisms in combination with the PI3K pathway would in principle lead to stronger and more durable antitumor activity.

In this proposal we aim to validate in the laboratory theoretical predictions of successful drug combinations. These predictions are obtained from mathematical models developed from what is currently known about the perturbations of the PI3K/AKT signaling network in response to different inhibitors of the pathway. In addition, we plan to test therapeutic combinations based on genomic analyses from tissue samples of breast cancer patients treated with PI3K inhibitors.

Taken together, our results should provide the rationale to test novel and more effective therapeutic options for patients with hyperactivation of the PI3K pathway.