An international team of investigators from centers in the United States and the United Kingdom, including Weill Cornell Medical College, have been awarded a grant for $10 million over a three-year period to study the molecular underpinnings of metastatic prostate cancer while creating a comprehensive testing system to optimize personalized treatments.
Stand Up To Cancer (SU2C) and the Prostate Cancer Foundation (PCF), along with the American Association for Cancer Researc, SU2C’s scientific partner, announced the formation of a new “Dream Team” dedicated to prostate cancer research.
One of the project’s goals is to try to understand why therapies can become ineffective, despite working initially, and if patients may be treated with other types of therapies or participate in clinical trials. The researchers plan to develop cell line models to study tumor mutations to determine, for example, if they are the culprit behind such cancer recurrences in patients. In addition, the investigators plan to study novel combinations of drugs in clinical trials, including exploring the use of PARP inhibitors and drugs that inhibit the PTEN pathway, which is involved in cell signaling and growth. PTEN is a well known tumor suppressor gene. PARP inhibitors prevent an enzyme involved in DNA repair, especially in the repair of tumor cells, from working.
Dr. Himisha Beltran of the Weill Cornell Prostate Cancer Program and Dr. Mark A. Rubin, Professor of Pathology and Laboratory Medicine, are leading researchers at Weill Cornell who, along with an international team of researchers, have discovered an Achilles’ heel in an aggressive type of prostate cancer — a vulnerability they say can be attacked by a targeted drug that is already in clinical trials to treat other types of cancers.
In the findings, published in Cancer Discovery, the researchers report that the investigational drug had a dramatic response in animal models of neuroendocrine prostate cancer, and so provides the first hope of an effective human therapy for this lethal cancer. Although neuroendocrine prostate cancer comprises only 2% of initial prostate cancer diagnoses, patients can progress from a more common prostate cancer to a neuroendocrine form as their cancer becomes more advanced.
Specifically, Drs. Beltran and Rubin have discovered that the aurora kinase inhibitor PHA-739358 works against human neuroendocrine prostate cells. To date, the more common adenocarcinoma prostate cancer is treated via androgen suppression therapy. This treatment is utilized well for the more common prostate cancer. But, it is speculated that as the androgen suppression therapy destroys the common cancer cells, neuroendocrine prostate cancer cells grow in their place. If ongoing research confirms this hypothesis, this new molecular pathway could offer hope for the treatment of neuroendocrine prostate cancer.