Lipid Elongation via ELOVL5: A Novel Target for Advanced Prostate Cancer
Abstract
Prostate cancer is a significant public health issue in Western countries, being the most commonly diagnosed cancer and the second-leading cause of cancer-related death in men. The growth of prostate cancer requires hormones called androgens, an example of which is testosterone. Besides surgery to remove the prostate, therapies for prostate cancer generally work to block androgen production or androgen action to prevent their growth-promoting effects in prostate cancer cells. However, unfortunately, most tumours develop resistance to these therapies and they continue to grow, despite androgen blockade. This type of prostate cancer is called castration-resistant prostate cancer and is lethal. We urgently need to better understand the molecular processes that happen in prostate cancer cells to design better drugs that prevent death from this disease. Our preliminary data show that lipids are important molecules in prostate cancer. Lipids are a class of molecules that make up cell membranes and are an important source of energy for cells. Changes in lipids occur during prostate cancer progression, most prominently in a process called lipid elongation, which requires enzymes called elongases. Our team has shown that one of these enzymes, called ELOVL5, is critical in prostate cancer. This project aims to investigate how ELOVL5 works in prostate cancer and whether stopping ELOVL5 from working in prostate cancer cells would be an effective treatment for patients. Our objective is to better understand the lipid elongation process, including how it affects prostate cancer growth, and inform development of new prostate cancer drugs that target lipid elongation. Despite being a fundamental process in cancer cells, this will be the first study that explores lipid elongation and how it contributes to prostate cancer and therapy resistance. A unique strength of our team is that we bring together recognised expertise in prostate cancer and lipid biology, capability in state-of-the-art laboratory techniques, access to large patient cohorts, and established mouse and patient-derived experimental models. The use of samples from prostate cancer patients in our research will ensure we make significant inroads into understanding lipid elongation and how it can be therapeutically exploited. Importantly, it will greatly accelerate the time required to develop a new drug that can be used to help prostate cancer patients, particularly those with castration-resistant prostate cancer, and prevent or reverse the onset of lethal disease.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910566
Entities
People
- Massimo Loda
Organizations
- NewYork–Presbyterian Hospital
- United States Army