As a V Foundation MVP, Guy T Phillips Honors His Wife
Find out moreState: Indiana
Zachary T. Schafer, Ph.D.
Funded by Hooters of America
In honor of Milly Longmire
Tao Lu, Ph.D.
Funded by the Kay Yow Cancer Fund
Ovarian cancer (OC) is the deadliest gynecological cancer. The standard treatment approach for epithelial OC is the combination of a platinum compound, mainly carboplatin and taxane. Although most women initially respond well to treatment, the vast majority experience disease recurrence within 2 years, resulting in a fatal relapse due to chemoresistance. Thus, the development of carboplatin resistance is a major barrier in OC treatment. To date, no effective approaches have been developed to overcome carboplatin resistance. We hypothesize that high expressions of some key proteins lead to carboplatin resistance in OC. Recently, we have developed the innovative validation-based insertional mutagenesis (VBIM) technique for novel gene discovery. In this proposal, our overall objective is to use the VBIM technique, in combination with bioinformatics and other advanced approaches, to identify key proteins that lead to carboplatin resistance in OC cells. Human OC cell lines and OC tumor tissues will be used as our research tools. Overall, our unique and comprehensive approach could yield a set of completely novel carboplatin resistance proteins which might not be discovered using traditional methods. The important findings generated from this work will guide physicians to design more rational and precise therapies with greater effectiveness in a specific OC patient. Moreover, this work could open future opportunities for reversal of carboplatin resistance by developing small molecule inhibitors. Therefore, this work would have a fundamentally transformative effect on OC chemotherapy.
Emily Dykhuizen, Ph.D.
V Scholar Plus Award- extended funding for exceptional V Scholars
Kidney cancer is the 8th most common cancer in the USA. Clear cell renal cell carcinoma (ccRCC) is the most common and lethal type of kidney cancer. If ccRCC spreads from the kidney, it becomes incredibly deadly. In addition, the drugs that successfully treat other cancers have no effect on the tumors. The most common gene mutation in ccRCC was discovered over 20 years ago. Figuring out the function of this gene led to the first drugs that successfully treat ccRCC. While this has improved the outcome for ccRCC patients, they still only survive an average of 22 months. Additionally, some patients do not respond to these drugs at all. We need to better understand what makes ccRCC different than other cancers. In addition, we need to understand what makes some ccRCC patients different than other ccRCC patients. Our lab studies a protein called Polybromo-1, which is the second most commonly mutated gene in ccRCC. Our goal is to understand how ccRCC patients with mutations in this gene are unique. From this information, we will figure out how to treat this set of patients using new drugs.
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