Developing a New Method to Optimize Cancer Drugs

What biomedical issue did you address in your research and what did your studies find?

My Ph.D. research focused on identifying new drug combinations that will work well together in treating cancer. Cancer is rarely treated with a single pharmacological agent. Instead, doctors rely on combinations of drugs that interact with each other synergistically to kill cancer cells, evade the body's acquired resistance to treatment and reduce potential toxic side effects. However, identifying and verifying new drug combinations for cancer treatment is complex. My thesis project approached this problem with a three-step strategy. Utilizing many new publicly available datasets, I used a computational approach to identify new agents that might work together to destroy cancer cells. I used experimental approaches to verify the most promising drug combinations in a variety of cancer model systems. I then investigated the underlying biological mechanisms to determine why a particular drug combination was working well together.

Through this research strategy, we identified a specific combination of enzyme-inhibiting drugs — in particular, a combination of drugs known as PARP inhibitors, which halt DNA repair, and Aurora Kinase inhibitors, which are involved in the cell cycle — that seems to have a synergistic effect when used together against prostate cancer cells. Further, we found that PARP inhibitors and Aurora Kinase inhibitors seem to function through ferroptosis — a recently described mode of cell death — by dual targeting the antioxidant and iron-reduction pathways, respectively, and not through mechanisms that have been previously postulated. Ultimately, this project helped identify new potential combinations for cancer treatment and new mechanisms through which PARP and Aurora Kinases might work. In addition, our findings helped to better reveal the importance of ferroptosis in prostate cancer.

What aspects of Mayo's culture helped you grow as a scientist and as a thinker?

One of the most rewarding experiences for me was mentoring students in the Summer Undergraduate Research Fellowship (SURF) program. Over the years, I mentored four SURF students who joined Dr. Wang's lab through the Molecular Pharmacology and Experimental Therapeutics track, as well as students in other areas. Being a mentor was meaningful in several ways. One was giving back: I had help on my path to a Ph.D., and it felt good to pass along the favor to the next generation of up-and-coming scientists. Also, I hope to manage research teams in the future, and working with students on their projects helped reinforce my communication and leadership skills in the context of scientific exploration.

What's next?

In my next steps, I hope to continue my exploration of leading cancer pharmacology projects, but now with a sense of confidence that I am educated in my field and able to pick up new skills as the projects require. My time at Mayo let me explore many topics, but ultimately, cancer pharmacology is still what excites me most.