Targeting PI3-kinase (PI3K), AKT and mTOR axis in lymphoma

Targeted therapy represents a transformation in oncology, a field that has relied primarily on non-selective cytotoxic therapies. Phosphatidylinositol 3-kinase (PI3K) is a family of ubiquitous signalling molecules involved in a wide variety of cellular processes and likewise, in a broad selection of human cancers. The discovery that the p110- form of PI3K is differentially expressed in normal and malignant lymphocytes has led to the development of specific inhibitors that are currently in clinical trials for lymphoma. Downstream effectors of PI3K, including v-akt murine thymoma viral oncogene homolog 1 (AKT; also termed AKT1) and mechanistic target of rapamycin (serine/threonine kinase) (mTOR) are similarly important in lymphoma, and agents targeting these components of the PI3K-AKT-mTOR axis are also underway, although at earlier stages of development. In this review we examine the role of PI3K-AKT-mTOR in normal and malignant lymphocytes, as well as the preclinical and clinical status of a number of inhibitors of this pathway.