Using high-performance computing to develop and test new cancer therapies
A mother and a mentor inspired Dr. Sunil Sharma to become an oncologist, but it is the challenge of cancer that continues to push him onward.
“When I was looking at my specialization, oncology was very attractive because there was a lot of science being done, but the therapeutic challenge hadn’t been met yet,” he recalled. “There was a whole unmet challenge in medicine that I wanted to be part of.”
Today, Dr. Sharma faces these challenges head-on at TGen as the newly appointed Deputy Director of TGen Clinical Sciences, Professor and Division Director of Applied Cancer Research and Drug Discovery. He is also Professor of Medicine at City of Hope and Chief of Translational Oncology and Drug Development at HonorHealth Research Institute in Scottsdale.
In his new roles, he stands on the shoulders of two giants: His mother, Dr. Urmil Sharma, and his mentor, Dr. Daniel D. Von Hoff, TGen Distinguished Professor and Physician-in-Chief.
A true pioneer, Dr. Urmil Sharma was the first woman from India to receive a fellowship at the Royal College of Radiologists in England. Following her training, she returned to India and ultimately retired as a dean at the All India Institute of Medical Sciences — what many consider to be the Harvard of India.
“She was my hero and the person that inspired me to go into medicine,” Dr. Sharma explained. “She was a mold-breaker as a woman — to be educated abroad in the 1960s and then come back and basically set up oncology in India. There are hundreds of thousands of people that she had a hand in training.”
When he was applying for fellowships of his own in the 1990s, Dr. Sharma turned down a prestigious opportunity at M.D. Anderson Cancer Center to go to the University of Texas-San Antonio and work with Dr. Von Hoff on Phase 1 clinical trials
and drug development.
“I have had the gratifying responsibility of helping train more than 2,200 budding cancer doctors,” said Dr. Von Hoff, who also serves as Chief Scientific Officer and the Virginia G. Piper Distinguished Chair for Innovative Cancer Research at HonorHealth. “I couldn’t be more excited to have one of my top students, and now an esteemed colleague, Dr. Sharma, join me in pursuing the use of genomic science to help bring precision medicine solutions to our patients.”
The Sharma lab will collaborate with Dr. Von Hoff in the clinic and also on new approaches to colon and pancreas cancer.
Dr. Sharma is also focused on cancers that lack effective therapies: adrenocortical carcinoma (ACC) and small cell carcinoma of the ovary, hypercalcemic type (SCCOHT). Both are rare and deadly cancers where TGen scientists have made recent discoveries. The next step is translating those discoveries into patient benefit.
For ACC, Dr. Sharma is working closely with patient advocacy groups and TGen Foundation to launch new clinical trials with our partners at HonorHealth and Baylor Research Institute in Dallas.
“We don’t like to work on things that have an obvious solution already. If there are existing drugs that are good, they can use those drugs,” explained Dr. Sharma, who came to TGen after nine years at the Huntsman Cancer Institute in Utah. “There are a large number of druggable proteins that haven’t been worked on, and we want to contribute in a way that is going to add to the repertoire for cancer therapy.”
With Research Associate Professor Dr. Hariprasad Vankayalapati and Research Assistant Professor Dr. Mohan Kaadige, the Sharma Lab uses high-performance computing to design and test virtual drugs on targeted proteins. They then synthesize the compounds “in real life” and test the computer hypothesis in the lab, going back and forth between the real and virtual worlds
to determine their effectiveness on the challenge
Their innovative process works: Dr. Sharma helped launch two drug development firms, Beta Cat Pharmaceuticals and Salarius Pharmaceuticals. While working for Swiss-based Novartis, he helped develop anti-lung cancer drugs and immunotherapies that activate the body’s own immune system against cancer cells.
One challenge Dr. Sharma would like to investigate is also very personal: In the last two years, his mother was diagnosed with Alzheimer’s disease. He has started discussions with Dr. Matt Huentelman, TGen Professor of Neurogenomics, about his research into the sixth-leading cause of death in the United States.
“This is personal to me, but it’s also a problem that TGen is working on,” Dr. Sharma said. “We feel like we’re experts in building drugs, but on the other hand, we can’t be domain experts on the biology and the things to go after. We can make drugs for Alzheimer’s, but we can’t be the experts on Alzheimer’s. The urgency that TGen has to get these advances into the clinic is attractive, and TGen has the ecosystem to develop these ideas.”