Development of lipogenesis inhibitors for tumor regression in renal cell carcinoma and other MYC-driven cancers

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SUMMARY: Over 400,000 new cases of renal cell carcinoma (RCC) are detected annually worldwide. One-fourth of these patients are already in advanced stages when diagnosed; with current therapies, their predicted 5-year survival rate is only 12%. To help curtail this loss of life, Bacchus Therapeutics has created a family of novel molecules that cause regression of tumors in preclinical animal models of RCC. These potential therapeutics provided long- term survival, rather than merely delaying tumor growth. These compounds also showed potency against other cancers driven by the MYC oncogene, including hepatocellular carcinoma and B-cell lymphoma. The goal of the proposed Phase I SBIR project is to characterize the biochemical traits and cytotoxicity of 7 candidate molecules, which will determine a lead candidate for development into an effective drug against RCC. Initial studies will define the solubility of the molecules, as well as specificity for their target enzyme. Additional work will evaluate their relative toxicity to RCC versus normal cell lines. Based on these results, the candidate with the highest specific potency will be tested in mouse models of RCC, using patient-derived xenografts that express either high or low levels of MYC. Following the successful completion of these Aims, we will seek Phase II SBIR funding to undertake studies that will enable Investigational New Drug development. Through partnering or licensing, we plan to commercialize the lead compounds as a completely new therapeutic agent against advanced RCC. Future work will evaluate this molecule or related analogs for treatment of other MYC-driven cancers.