A study published by Nature has defined the function of p110 alpha, the flag-ship molecule of the eight member PI3K family, which is one of the most frequently activated pathways in cancer.
The function of p110 alpha in the body has eluded researchers for over a decade but a new approach to generating mouse models, has allowed investigators from the Ludwig Institute for Cancer Research's (LICR) UCL Branch and the UCL Centre for Diabetes & Endocrinology to solve the mystery and yield important information for planned clinical trials with PI3K inhibitors.
The study showed that p110 alpha controls the action of insulin and other key hormonal signals that play roles in growth, diabetes and obesity. p110 alpha is frequently mutated or overexpressed in cancer, and the results of the present work imply that cancer cells hijack a key signalling pathway to fuel their energy needs and drive their proliferation and survival. The current work has far-reaching implications, given that several million of people are affected by metabolic disorders, and every year, several hundreds of thousand new cancer cases with mutations in p110 alpha are diagnosed.
Importantly, says LICR's Dr. Bart Vanhaesebroeck, the senior author of the study, the findings have immediate implications for the testing of p110 alpha-specific inhibitors for human therapies. "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. These mice mimic the effect of systemic administration with a p110 alpha-specific drug,"