Targeting neural transcription factor BRN2 in neuroendocrine tumours
One in eight men in Canada will be diagnosed with prostate cancer in their lifetime. Despite the availability of surgical, radiological and drug treatment options, many patients develop castration resistant prostate cancer (CRPC), an incurable disease which is especially resistant to drugs. In its most lethal form, drug resistant CRPC behaves like a neuroendocrine cancer, which is completely unresponsive to traditional prostate cancer therapies.
In his model of drug resistant CRPC, Dr. Munuganti has identified a molecular pathway that appears to be essential for prostate cancer to take on neuroendocrine features. A key protein in this pathway, BRN2, is high in patients with neuroendocrine prostate cancer and is critical for neuroendocrine tumour growth in a laboratory model. BRN2 expression also plays a critical role in other neuroendocrine cancers such as small cell lung cancer and Ewing sarcoma. There is an urgent need to develop drugs that have the ability to inhibit the function of BRN2 for the treatment of patients with deadly neuroendocrine tumors.
Using high-powered and intelligently designed computer models, Dr. Munuganti has developed drug prototypes that have the ability to prevent BRN2 from supporting neuroendocrine cancer cell growth in our laboratory models. Dr. Munuganti’s study will fine-tune the drug-like properties of the leading BRN2 inhibitors and test them in biological models of neuroendocrine cancers. The results of this research could lead to the development of new therapies capable of reducing or slowing the growth of lethal neuroendocrine cancers, substantially improving patient survival.
Findings will be presented at conferences and seminars such as AACR Annual Meetings and the ASCO Annual Meeting, providing an opportunity to exchange ideas with other researchers and clinicians in the field and opening up possible collaborations. The ultimate goal of this study will be to commercialize a BRN2 inhibitor for patients suffering from no-cure neuroendocrine tumours.