Combinatorial Inhibition of MYC in Prostate Cancer
Abstract
Reason and Logic for the Study: Prostate cancer is dependent on the male hormones in the body, and the mainstay of treatment in men with advanced prostate cancer is depriving the body of the male hormones. Unfortunately, the hormone deprivation treatment does not work in all men; in fact, the treatment works only for a limited period of time for most men. Therefore, there is an urgent and desperate need to develop new treatment options that can be delivered either instead of or with hormone deprivation treatment. Contribution to the Science of Prostate Cancer: Cancer is a disease that is caused by severe genetic alterations. One of the cancer-causing genes that is most highly expressed (about 75%) in most human cancers, including the prostate, is called c-MYC. While targeting MYC for treatment seems an obvious choice, efforts to date have been unsuccessful because of the complex protein structure that is not friendly to drug development. Interestingly, MYC cannot work on its own in the body and needs a partner called MAX to function. The novelty of this proposal is, instead of directly targeting MYC, which is impossible, we will target the interaction between MYC and MAX, resulting in reduced MYC function. This novel idea is possible because of better understanding of how MYC and MAX work as partners and development of new types of drugs: small molecules and decoy proteins that prevent MYC partnering with MAX. What Types of Patient Will the Study Help? All men with advanced prostate cancer will be helped with this new treatment. The treatment will be particularly effective in men for whom standard treatment, such as deprivation of male hormones, does not work or has stopped working. How Will the Treatment Help the Patients? We generally treat cancer patients for one or more of the following three reasons: (1) to make men with prostate cancer live longer; (2) to prevent prostate cancer from getting worse, such as spreading to other parts of the body or causing urine blockage; (3) to make symptoms from prostate cancer go away. Because the MYC works excessively in men with prostate cancer, treating men with the novel drug will help with all three of the goals above. Potential clinical applications, benefits, and risks: The proposal will establish the safety and efficacy of the novel drugs that inhibit MYC, heralding a new class of drugs for men with advanced prostate cancer. The study will generate sufficient data to get approval from the Food and Drug Administration to study the novel drugs in humans for the first time. However, there are risks. Because MYC is expressed in other parts of the body as well and is necessary for a healthy body, there may be undesirable side effects that need to be studied carefully. Timeline for Use in Patients: If all works out as expected, the novel drugs can be tested in humans within 5 years. Several major and critical developments are done: drug development and testing effectiveness on prostate cancer cells in the laboratory. The steps proposed in the proposal will expedite advancement of the drugs to human use by studying the safety and efficacy in animals that carry prostate cancer, identifying the correct dose and number of times a day the drug needs to be given, and helping recognize and anticipate any major undesirable side effects in humans.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910745
Entities
People
- K.C. Balaji
Organizations
- United States Army
- University of Florida