PI3K pathway alterations in cancer: variations on a theme

TL Yuan, LC Cantley - Oncogene, 2008 - nature.com
TL Yuan, LC Cantley
Oncogene, 2008nature.com
The high frequency of phosphoinositide 3-kinase (PI3K) pathway alterations in cancer has
led to a surge in the development of PI3K inhibitors. Many of these targeted therapies are
currently in clinical trials and show great promise for the treatment of PI3K-addicted tumors.
These recent developments call for a re-evaluation of the oncogenic mechanisms behind
PI3K pathway alterations. This pathway is unique in that every major node is frequently
mutated or amplified in a wide variety of solid tumors. Receptor tyrosine kinases upstream of …
Abstract
The high frequency of phosphoinositide 3-kinase (PI3K) pathway alterations in cancer has led to a surge in the development of PI3K inhibitors. Many of these targeted therapies are currently in clinical trials and show great promise for the treatment of PI3K-addicted tumors. These recent developments call for a re-evaluation of the oncogenic mechanisms behind PI3K pathway alterations. This pathway is unique in that every major node is frequently mutated or amplified in a wide variety of solid tumors. Receptor tyrosine kinases upstream of PI3K, the p110α catalytic subunit of PI3K, the downstream kinase, AKT, and the negative regulator, PTEN, are all frequently altered in cancer. In this review, we will examine the oncogenic properties of these genetic alterations to understand whether they are redundant or distinct and propose treatment strategies tailored for these genetic lesions.
nature.com