Stand Up To Cancer

Scientists on SU2C's PI3K Dream Team made a significant research finding that was recently published in the online edition of Nature Medicine (pp1-6). These findings could accelerate the development of targeted therapies for treatment-resistant breast cancers. Dream Team scientists have identified a gene that may play a key role in breast cancers that become resistant to PI3K-pathway targeted therapy.

The PI3K pathway helps regulate cell survival and growth, and, as such, plays a key role in the development of a variety of cancers including breast, colon and many other types. Researchers hope that drugs targeting this pathway could lead to more effective therapy. However, like many cancer therapies, treatments that inhibit the PI3K pathway also face one of the most significant challenges facing cancer researchers today - treatment resistance.

Unfortunately, resistance to treatment is usually identified after the patient no longer responds to treatment; and with breast cancer that usually means the tumor has grown. This is not only costly, but patients have been subjected to therapies that ultimately couldn't help them, therapies that could have significant side effects impacting their quality of life, and - perhaps most importantly - patients have lost time in identifying other therapies that could possibly produce better results in treating their cancers.

Scientists have been working to identify the genes that regulate the PI3K pathway and have made progress - however - clearly there are still mechanisms that are driving PI3K resistance. Through preclinical studies, scientists on the SU2C PI3K Dream Team believe they have identified a potential mechanism for resistance in breast cancer mediated by the PIK3CA gene, which encodes a protein subunit of PI3K.

Led by Jean J. Zhao, Ph.D., an assistant professor in the department of Cancer Biology at Dana-Farber Cancer Institute and the department of Pathology Harvard Medical School, researchers generated a genetically engineered mouse model of human breast cancer to identify genes that cause resistance to PI3K pathway inhibitors and found that one such gene called Myc seems to be crucial. Results indicated that those with multiple copies of Myc were more likely to resist therapy than those that did not have multiple copies of the gene. In addition, greater amplification of the Myc gene seemed to be associated with development of a pathway independent of PI3K, which would ultimately negate some of the anticancer effects of PI3K pathway inhibitors.

This finding will allow researchers to develop therapies that specifically target Myc. Findings also suggest that combination therapies targeting both PI3K and c-MYC may be necessary to circumvent resistance to PI3K targeted therapy.