title: MEK and PI3K inhibition in solid tumors: rationale and evidence to date.
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.
authors.affiliation: Department of Oncology and Radiotherapy, Oulu University Hospital, Oulu, Finland, PB20, 90029 OYS.
authors.forename: E
authors.initials: E
authors.lastname: Jokinen
authors.affiliation: Department of Oncology and Radiotherapy, Oulu University Hospital, Oulu, Finland.
authors.forename: J P
authors.initials: JP
authors.lastname: Koivunen
keywords: MEK; PI3K; inhibition; solid tumors; targeted therapy