FCMHW PROGRAM: Fatty acid oxidation inhibition to treat advanced prostate cancer
Contact: Dr Zeyad Nassar
Overview:
Our research has confirmed that prostate cancer cells are particularly good at activating a process called fatty acid oxidation to generate the energy that facilitates cancer cell proliferation, resistance of the cancer cells to drug therapies, and change cancer cell gene expression that allows them to progress to a more aggressive form.
We have identified two enzyme proteins, HADHB and DECR1 which are involved in this fatty acid oxidation in prostate cancer cells, and these proteins are most abundant in prostate cancer in men when the disease has progressed. With progression men are no longer responding to the standard anti-androgen drug therapy. Blocking these HADHB or DECR1 enzymes with a fatty acid oxidation inhibitor “starves” prostate cancer cells, overcomes drug resistance, and slows cancer tumour growth and metastasis.
While developing new drugs often can take 15 years, this program will reduce this timeframe by aiming to re-purpose existing lipid-modifying medicines because we know that existing approved drugs are safe and we understand how they behave and are distributed in the human body. A drug inhibitor is available for HADHB called trimetazidine, which is currently used to treat the heart disease condition, angina. We therefore aim to take our laboratory findings into a proof-of-concept clinical trial to test whether trimetazidine is safe and effective in treating men on ADT, to prevent or delay the onset of lethal castrate resistant prostate cancer.
Through this trial we aim for a potential new therapeutic approach using existing drugs used to treat cardio-metabolic disease to prevent lethal prostate cancer, reduced drug-related toxicities in men being treated for prostate cancer, and Improved length and quality of life for men living with advanced prostate cancer.