MEK and PI3K Inhibition in Solid Tumors: Rationale and Evidence to Date

Ther Adv Med Oncol. 2015 May;7(3):170-80. doi: 10.1177/1758834015571111.

Abstract

PI3K-AKT-mTOR and Ras-Raf-MEK-ERK are the most commonly altered oncogenic pathways in solid malignancies. There has been a lot of enthusiasm to develop inhibitors to these pathways for cancer therapy. Unfortunately, the antitumor activities of single-agent therapies have generally been disappointing, excluding B-Raf mutant melanoma and renal cell cancer. Preclinical studies have suggested that concurrent targeting of the PI3K-AKT-mTOR and Ras-Raf-MEK-ERK pathways is an active combination in various solid malignancies. In the current work, we review the preclinical data of the PI3K and MEK dual targeting as a cancer therapy and the results of early-phase clinical trials, and propose future directions.

Keywords: MEK; PI3K; inhibition; solid tumors; targeted therapy.

Publication types

  • Review