MYC is a critical protein in cancer and a promising drug target. Theoretically, a drug that can inhibit MYC’s activities is suitable for treating 75% of human cancer cases. However, there is no FDA-approved MYC inhibitor yet, which is a prominent gap in current cancer therapy. The technological challenge for developing such a drug is that MYC is a unique protein that has no stable structure; therefore, MYC is not a suitable target for traditional drug development processes. To overcome this problem, we have recently developed unique molecules that can bind to structure-less proteins. As a proof-of-concept, we demonstrated a molecule that efficiently acted on MYC in brain cancer cells and halted cell proliferation. In this proposal, we seek to improve the performance of this molecule and develop potent drugs that can inhibit MYC.

Our Research Plan Consists of Three Parts. First, we will synthesize 12 million molecules; each of them exhibits a unique three-dimensional structure. From this pool of molecules, we will find those that have the potential to become MYC-specific drugs. Second, we will chemically modify those identified molecules to make them suitable for preclinical and clinical testing. Third, we will test those drugs in brain cancer cells to evaluate their therapeutic effects. We will study the potential drug resistance mechanism and develop methods to overcome it.

Successful completion of the proposed work will generate drug molecules that are ready for preclinical and clinical testing. If these drugs are proven effective in clinical trials, they can be used to treat many types of cancers, including colorectal cancer, esophageal cancer, head and neck cancer, stomach cancer, liver cancer, and brain cancer. Additionally, the knowledge generated in this study provides a deeper understanding of how the most lethal type of brain cancer – glioblastoma – respond to this type of treatment. Currently, there is no cure or effective therapy for glioblastoma, and the average survival time after diagnosis is less than 6 months. Our study can immediately bring hope to those Service members, their families, Veterans, or other beneficiaries that are affected by glioblastoma.

The proposed work aligns well with the PI’s long-term goal, which is to develop a panel of cancer drugs that tackle those previously undruggable oncogenic proteins. His immediate focus is the proteins that are implicated in highly lethal cancer types, such as brain cancer and metastatic cancers. Also, the unique mechanism of the VCC Scholar Award is a platform for the PI to expand his knowledge in cancer biology, network and collaborate with well-established cancer researchers, promote his expertise and scientific ideas, and build leadership skills. All of these activities will provide the PI with the opportunity to advance his career at the forefront of cancer research.