Enzyme That Sensitizes Cells To Chemotherapeutics Could Also Be New Anti-cancer Target

Main Category: Cancer / Oncology
Also Included In: Lung Cancer
Article Date: 20 Aug 2008 - 3:00 PDT

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Researchers at Van Andel Institute (VAI) and Novartis Institutes for Biomedical Research have identified an important enzyme required for cancer cell survival. Lowering levels of the enzyme caused a wide variety of cancer cells to die, reduced proliferation of cancer cells, and sensitized cancer cells to commonly used chemotherapeutic agents, such as the drug Taxol. The cells in the study included pancreatic, prostate, and lung cancer cells.

"We have identified a previously unrecognized anti-cancer target," said VAI Scientific Investigator Jeff MacKeigan, Ph.D. "For some reason, cancer cells become 'addicted' to certain genes. When we blocked the gene that results in the enzyme PI3K-C2alpha using a fairly new tool used extensively by our lab called RNA interference, we found this had an abrupt adverse effect on a variety of cancer cells."

The findings, published in Molecular Cancer Research, examined the role of an often overlooked class of phosphoinositide 3-kinase enzymes and found that one of the enzymes, called PI3K-C2alpha, was required for several types of cancer cells to survive. Researchers found that lowering levels of this enzyme reduced proliferation in a number of cancer cell lines, and they were able to determine a critical threshold level of PI3K-C2alpha below which cell death was "switched on."

"Although we must further determine what happens in normal cells to confirm the therapeutic value, we also found that decreasing levels of PI3K-Class 2 alpha to a certain point didn't kill the cancer cells, but did sensitize them to chemotherapeutic agents such as Taxol," said MacKeigan. "This alone could contribute to a more effective anti-cancer strategy in a subset of cancers."

Established by Jay and Betty Van Andel in 1996, Van Andel Institute is an independent research organization dedicated to preserving, enhancing and expanding the frontiers of medical science, and to achieving excellence in education by probing fundamental issues of education and the learning process.

Van Andel Institute