Mutated Protein in Cancer Found in Diabetes

[Angel]

After eluding researchers for more than a decade, a new study solves the mystery of the function of one of the most frequently mutated proteins in cancer. It defines the role of p110 alpha, the flagship molecule of the eight-member PI3K family.

Researchers in England found p110 alpha controls the action of insulin and other important hormones involved in growth, diabetes and obesity. The protein is often mutated in cancer. Results imply the cancer cells hijack a key signaling pathway, to fuel their energy needs and drive their proliferation and survival.

These findings have immediate implications for the testing of p110 alpha-specific inhibitors for new treatments. "Accurate information on the specific role of p110 alpha is needed urgently by the pharmaceutical industry, which is preparing to initiate clinical trials based on PI3K inhibition, not only in cancer but also in inflammation, allergy and auto-immunity," says Bart Vanhaesebroeck, Ph.D., the senior study author. "These mice mimic the effect of systemic administration with a p110 alpha-specific drug."

Researchers say traditional mouse models have been engineered to completely remove the p110 alpha gene. This study introduced a single mutation that inactivates but does not remove the protein. Results show the mice were smaller, but ate more and had greater levels of body fat. They also had higher insulin levels and were glucose-intolerant but did not develop full diabetes. This suggests drugs that block p110 alpha function in cancer cells, may not have the severe metabolic disturbances first expected.