Development of phosphoinositide-3 kinase pathway inhibitors for advanced cancer.
The phosphoinositide-3 kinase (PI3K) pathway plays a critical role in cancer cell growth and survival. PI3K is activated in human cancers by elevated receptor tyrosine kinase activity, RAS mutation, as well as by mutation, amplification, and deletion of genes encoding components of the pathway. Additionally, PI3K pathway activation plays an important role in acquired resistance to both chemotherapy and targeted agents. The essential role of PI3K in human cancer has led to the development of PI3K pathway inhibitors that have shown promise in preclinical models and have entered phase 1 clinical trials. This article reviews preclinical and clinical data on members of this novel drug class, as well as data justifying the combination of PI3K inhibitors with other anticancer agents.
Cleary
James M
JM
Department of Medical Oncology, Early Drug Development Center, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA, 02115, USA.
Shapiro
Geoffrey I
GI
D000818:Animals; D002986:Clinical Trials as Topic; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*
D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors