New Approach to Treatment Resistance in Head and Neck Cancers

February 2013, Vol 4, No 2 - Value Propositions

The majority of head and neck tumors are associated with a deregulation of the PI3K/AKT/mTOR pathway, which has until now been seen as the culprit in treatment resistance in these cancers. However, new data recently published in Cancer Research show that this pathway is not necessarily the reason for tumor progression in this type of cancers. Because head and neck cancers are very heterogeneous, new research has focused on identifying the various drivers of tumor survival to understand why mTOR inhibitors only work in a few patients. “While a few tumors are dependent only on mTOR, others are dependent on both mTOR and AKT,” according to Pradip K. Majumder, PhD, Division of Cancer Biology, Mitra Biotech, Bangalore, India. “However, a majority of the mTOR pathway–activated tumors seemed to not be dependent on this axis for survival or maintenance.”

The use of targeted characterization of tumors resistant to dual AKT/mTOR inhibitors showed that multiple pathways were involved in the tumor proliferation and likely explain tumor survival. Dr Majumder and colleagues are now using a systems biology approach called “tumor explants model” to differentiate the actual drivers of various mutations from those known as “passenger” mutations, which do not influence tumor survival. This distinction is critical for understanding why many drugs fail in early-phase clinical trials, as well as for stratifying patients for appropriate treatments and for developing new combination therapies. “Using this approach, researchers may be able to develop a translational tool for further clinical development of novel anticancer drugs,” Dr Majumder said. AACR press release; January 29, 2013