Targeting Breast Cancers Featuring Activating Mutations in PIK3CA by Generating a Lethal Dose of PIP3; Annual summary rept. 1 Feb 2007-31 Jan 2008

摘要

Our research described here is relevant to the pathogenesis and a potential novel therapy for breast cancers. The PIK3CA is the most commonly mutated oncogene in breast cancer and loss of the tumor suppressor, PTEN, occurs frequently in patients suffering from this disease. The most significant accomplishment during the second year of funding is the mammary gland tumor model induced by conditional expression of an oncogenic PIK3CA allele which will allow us to determine the oncogenic role of PIK3CA in tumor initiation, progression, maintenance and metastasis etc. It should also significantly facilitate preclinical testing for the development of PI3K inhibitors for targeted therapy. Our final goal of simultaneous inactivation of PTEN and activation of PIK3CA will not only provide a new perspective on the relationship of the two key oncogene and tumor suppressor, PIK3CA and PTEN, and the signaling pathway under their control in cell regulation and oncogenic transformation, but also a potential novel therapy to all patients plagued with the common tumorigenic mutations.