Clinical development of phosphatidylinositol-3 kinase pathway inhibitors.
The PI3K pathway is the most commonly altered in human cancer. Several recent phase I studies with therapeutic inhibitors of this pathway have shown that pharmacological inhibition of PI3K in humans is feasible and overall well tolerated. Furthermore, there has already been clinical evidence of anti-tumor activity in patients with advanced cancer. The intensity and duration of PI3K inhibition required for an antitumor effect and the optimal pharmacodynamic biomarker(s) of pathway inactivation remain to be established. Preclinical and early clinical data support focusing on trials with PI3K inhibitors that are at a minimum enriched with patients with alterations in this signaling pathway. These inhibitors are likely to be more effective in combination with established and other novel molecular therapies.
Arteaga
Carlos L
CL
Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA. carlos.arteaga@vanderbilt.edu
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D055808:Drug Discovery; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D018579:Patient Selection; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects*
D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors