Targeting PI 3‐kinase ( PI 3 K ), AKT and m TOR axis in lymphoma

Summary Targeted therapy represents a transformation in oncology, a field that has relied primarily on non‐selective cytotoxic therapies. Phosphatidylinositol 3‐kinase ( PI 3 K ) 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‐δ form of PI 3 K 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 PI 3 K , including v‐akt murine thymoma viral oncogene homolog 1 ( AKT ; also termed AKT 1) and mechanistic target of rapamycin (serine/threonine kinase) (m TOR ) are similarly important in lymphoma, and agents targeting these components of the PI 3 K ‐ AKT ‐m TOR axis are also underway, although at earlier stages of development. In this review we examine the role of PI 3 K ‐ AKT ‐m TOR in normal and malignant lymphocytes, as well as the preclinical and clinical status of a number of inhibitors of this pathway.