Breast cancer may be ’uniquely sensitive’ to inhibitors of PI3K pathway

Because up to 75 percent of breast cancer patients have an abnormality in a specific cell signaling pathway, drugs that target different molecules along that pathway may be especially effective for treating the disease, says a researcher from The University of Texas M. D. Anderson Cancer Center.

A clearer picture is now emerging about the importance of the phosphatidylinositol 3 kinase (PI3K) pathway to breast cancer development, says Gordon Mills, M.D., Ph.D., a professor and chair of the Department of Molecular Therapeutics. This pathway, which is linked to critical growth factor receptors and is involved in programmed cell death, is aberrant at multiple levels in breast cancer, including mutations in PI3K itself or its many “downstream” players, such as PTEN, or AKT.

“There is a lot of crosstalk between the PI3K pathway and other pathways, a lot of feed-forward and feedback loops,” says Mills. “But I and others believe there are central nodes between these intersecting circles that can be effectively targeted with drugs.”

Only one PI3K pathway inhibitor is in use to date, but others are increasingly being developed and tested, says Mills, who is discussing the importance of this pathway at the annual San Antonio Breast Cancer Symposium meeting. “At least 20 different companies have recognized the importance of the pathway in breast cancer and are trying to develop drugs that target it.”

In the future, breast cancer tissue samples from newly diagnosed patients can be tested for their specific PI3K pathway abnormality in order to find a drug that zeroes in on what may be the cancer’s Achilles’ heel, Mills says. “Using those drugs in combination with other treatments such as chemotherapy may significantly advance breast cancer care,” he says.