Involvement of autophagy in the response of tumor cells to PtdIns3K inhibitors: therapeutic implications.

Abstract

The phosphoinositide 3-kinase (PI3K) pathway plays a crucial role in cell proliferation and survival and is frequently activated by genetic and epigenetic alterations in human cancer. An arsenal of pharmacological inhibitors of key signaling enzymes in this pathway, including class I(A) PI3K isoforms, has been developed in the past decade and several compounds have entered clinical testing in cancer patients. The PIK3CA/p110α isoform is the most studied enzyme of the family and a validated cancer target. The induction of autophagy by PI3K pathway inhibitors has been documented in various cancers, although a clear picture about the significance of this phenomenon is still missing, especially in the in vivo situation. A better understanding of the contribution of autophagy to the action of PI3K inhibitors on tumors cells is important, since it may limit or enhance the action of these compounds, depending on the cellular context.

• Authors: Alexandre Arcaro
• Journal: Autophagy (Autophagy) Vol. 9 Issue 4 Pg. 607-8 (Apr 2013) ISSN: 1554-8635 [Electronic] United States
• PMID: 23324613 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Phosphoinositide-3 Kinase Inhibitors
• Protein Kinase Inhibitors
• TOR Serine-Threonine Kinases

Topics

• Animals
• Apoptosis (drug effects)
• Autophagy (drug effects)
• Cell Line, Tumor
• Humans
• Neoplasms (drug therapy, enzymology, pathology)
• Phosphatidylinositol 3-Kinases (metabolism)
• Phosphoinositide-3 Kinase Inhibitors
• Protein Kinase Inhibitors (pharmacology, therapeutic use)
• Signal Transduction (drug effects)
• TOR Serine-Threonine Kinases (metabolism)