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Targeting PI 3‐kinase ( PI 3 K ), AKT and m TOR axis in lymphoma
Author(s) -
Blachly James S.,
Baiocchi Robert A.
Publication year - 2014
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.13065
Subject(s) - pi3k/akt/mtor pathway , protein kinase b , akt1 , cancer research , lymphoma , kinase , phosphatidylinositol , biology , phosphorylation , chemistry , microbiology and biotechnology , signal transduction , immunology
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.