Diana Cruz, a senior biology major, and law and society minor at the University of Pennsylvania, studied the repurposing of pharmaceutical inhibitors as a potential treatment for cancer.
Pharmaceuticals have previously been repurposed for uses beyond their first intended indication. These repurposed drugs have been incredibly useful and have not only reduced the cost to take a medication to market, but they have also cut down the time for patients to get access to potentially life-saving medication since the pharmaceuticals are already proven to be safe if they are FDA approved. This summer with the Broad was an unforgettable experience that provided me the opportunity to tell my own story in science. I am incredibly grateful for all of my new mentors and making an amazing network of rising and established scientists. However, drug repurposing has not been previously systematic. Thus, scientists at the Broad used PRISM, a high throughput drug sensitivity assay, which systematically tested the drug sensitivity of 578 human cancer cell lines to 4,581 drugs with the potential to be repurposed. Our group used the PRISM data set to further our goal of identifying inhibitors with anti-cancer potential and understand the medical contexts in which they worked the best. We decided to investigate the drug sensitivity in relation to the genome. We utilized the Achilles project which measured the cell growth/death of 990 human cancer cell lines in response to 17,645 separate gene knockdowns. We only used the cell lines that overlapped between the Achilles project and the PRISM project to correlate the genes with the medications. Then, I looked at a known oncogene, BRAF, to find the medications with high correlations and investigated to see other genes with high correlations. I found that bis(maltolato)oxovanadium(IV) (BMOV4) had a correlation value of 0.22 with BRAF and a correlation value of 0.34 with EGLN1. EGLN1 has previously been identified to be a potential target for ovarian cancer and melanoma and BRAF mutations are associated with skin cancer. Consistent with this, upon further analysis, I found that BMOV4 led to cell death in brain cancer, endometrial/uterine cancer, liver cancer, ovarian cancer, and skin cancer. There was a statistically different drug sensitivity when the cell line had a BRAF mutation (p-value<0.0005). Moreover, there was a significant correlation between EGLN1 expression and drug sensitivity (p-value<0.0005). In the future, BMOV4 should be investigated further for possible treatment of cancers with mutated BRAF and/or highly expressed EGLN1, such as in skin and ovarian cancer.
Project: The Repurposing Potential of bis(maltolato)oxovanadium(IV) for Cancer Therapy
Mentors: Andrew Boghossian Cancer Program, PRISM Lab
Dr. Alex Wang, Cancer Program, J.T. Neal Lab