PF-04691502 + exemestane

PF-04691502 + exemestane is a **combination therapy** consisting of PF-04691502, a potent, selective, dual inhibitor of class I phosphatidylinositol 3-kinase (PI3K) and mechanistic target of rapamycin (mTOR), and exemestane, an aromatase inhibitor. PF-04691502 targets all class I PI3K isoforms and mTOR serine/threonine kinase, blocking PI3K/AKT/mTOR pathway signaling and resulting in inhibition of tumor cell growth and survival. Exemestane irreversibly inhibits aromatase, decreasing estrogen production and thus the growth stimulus for estrogen receptor–positive breast cancer cells. The combination has been investigated to overcome acquired resistance to endocrine therapy in hormone receptor–positive, advanced breast cancer, with the rationale that simultaneous inhibition of PI3K/mTOR and estrogen synthesis more effectively suppresses cancer progression. The combination was studied in phase II clinical trials but the trials were withdrawn or not completed due to limited tolerability and toxicity[1][3][5][7].