Thanks to pioneering research on the monoamine oxidase-A enzyme (MAO-A) conducted by USC University Professor Jean C. Shih, it is already known that this particular gene plays a role in depression, autism, aggression and other mental illnesses. Now, Shih and her co-investigators are examining the role MAO-A plays in the progression of prostate cancer.
This new study is being funded by a 3-year, $579,499 grant awarded by the Department of Defense through its Prostate Cancer Research Program (PCRP). The PCRP aims to promote innovative research focused on eradicating prostate cancer, and funds “high risk-high impact” research that is geared toward developing treatments for the disease. Co-investigators on the project are USC Assistant Professor Bogdan Olenyuk, and Professor Haiyen Zhu and postdoctoral fellow Boyang Jason Wu, both of the Cedars Sinai Medical Center.
The investigators have already shown that increased MAO-A is associated with prostate cancer progression. Conversely, they’ve shown that the inhibition or silencing of MAO-A significantly reduces the growth of prostate cancer.
“The objective of this study is to determine the functional role of MAO-A in human prostate cancer progression and metastasis, and to evaluate the effectiveness of novel MAO-A inhibitors to target prostate cancer cells, with the promise of preventing and eradicating prostate cancer growth,” explained Shih who holds the Boyd P. and Elsie D. Welin Professorship in Pharmaceutical Sciences.
MAO-A inhibitors are successfully being used to treat other diseases linked to this enzyme, such as depression, so Shih believes the right inhibitors can treat prostate cancer growth and eventually eliminate the cancer all together.
The funding provided by the DOD will be used to investigate the role of MAO-A action in prostate cancer growth and progression. Specifically, the researchers will
study if combining a drug currently on the market, used as an MAO-A inhibitor to treat depression, with other new MAO-A inhibitor compounds will reduce the progression and metastasis of prostate cancer.
“Since MAO-A inhibitors are already used to treat depression, we can expedite the testing of our hypothesis,” said Shih.
The team work will conjugate the MAO-A inhibitors to a novel near infrared (NIR) dye. Using optical imaging, the scientists will be able to follow the location of the drug- dye conjugate as it moves through the host and within the tumors. This provides a tool for diagnosis and monitoring of tumor of growth. Further, incorporating the tumor-specific dyes, the MAO-A inhibitors can be carefully targeted to the cancer cells, minimizing unwanted side effects on healthy cells.
“Our goal is to translate our research findings into the clinic,” said Shih. “Ultimately, our aim is to reduce or eliminate the suffering and death attributed to prostate cancer.”