Journal
THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY
Volume 7, Issue 3, Pages 170-180Publisher
SAGE PUBLICATIONS LTD
DOI: 10.1177/1758834015571111
Keywords
inhibition; MEK; PI3K; solid tumors; targeted therapy
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Funding
- Cancer Society of Northern Finland
- Emil Aaltonen Foundation
- Finnish Foundation for Tuberculosis Resistance
- Finnish Oncological Society
- Oulu University Hospital
- Orion-Farmos Science Foundation
- Sigrid Juselius Foundation
- Thelma Makikyro foundation
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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.
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