Shilpa Gupta, MD – From Fellowship to Leadership in GU Oncology Research

Shilpa Gupta, MD, is the director of genitourinary medical oncology at the Taussig Cancer Institute and co-leader of the Genitourinary Oncology Program at the Cleveland Clinic. She is clinical professor of medicine at the Cleveland Clinic Lerner College of Medicine at Case Western Reserve University. Dr. Guptas is past chair of the Case Comprehensive Cancer Center Protocol Review and Monitoring Committee and current co-chair of the Hoosier Cancer Research Network Genitourinary Clinical Trial Working Group. Throughout her career, she has pioneered research initiatives that led to the development of novel therapeutics and biomarkers for optimizing patient outcomes in genitourinary (GU) cancers, with a focus on bladder cancer.

GU Oncology Now spoke with Dr. Gupta to trace the trajectory of her impactful career in GU oncology, from her early research endeavors to her current leadership positions at the Cleveland Clinic. She describes her unwavering commitment to advancing the field through innovative investigator-initiated trials and collaborative efforts in National Cancer Institute (NCI)-led trials, as well as her visionary outlook on upcoming trends and advancements in GU cancer care.

Why did you become a GU oncologist, and what inspired you to enter this field? Did you have any mentors or people who influenced you during your education?

Dr. Gupta: I did not have any mentors, but after my hematology-oncology fellowship at Thomas Jefferson University, I did a year of GU oncology research. We were studying the role of Stat5 in prostate cancer. During my fellowship, I found caring for patients with prostate and bladder cancers very interesting, especially given the limited treatment options available at the time. The variety within this field, including prostate, bladder, kidney, and testicular cancers, was also appealing to me.

Can you guide us through your career path, highlighting your journey to becoming the esteemed researcher and expert in GU oncology you are today?

Dr. Gupta: I completed my medical training at Lady Harding Medical College in New Delhi, India, where I received strong clinical and hands-on training. It was a very well-rounded experience, and we took care of patients from low socioeconomic backgrounds with limited resources, which meant relaying on our clinical skills and limiting the use of unnecessary expensive tests. I was also involved in the Pulse Polio program as a medical student. We did a door-to-door campaign to vaccinate kids against polio.

After my medical school training,  I worked at a large tertiary care private hospital in India and also helped lead the initiative to help set up electronic medical records at the Army Research and Referral Hospital in New Delhi. I had a desire to do further training in the United States, and after earning a master’s degree in health informatics at the University of Minnesota, I completed my residency in internal medicine at the University of Connecticut in 2007.

Following my residency, I split my fellowship between Georgetown University and Thomas Jefferson University, and I then did an additional year of a translational research fellowship in GU oncology at Thomas Jefferson University. In 2011, I began my first faculty position at the Moffitt Cancer Research Institute. During my time there, I was heavily involved in experimental therapeutics and had the opportunity to lead several high-impact trials in solid tumors, including KEYNOTE-012, which set the stage for immunotherapy in bladder cancer, among other cancers. I also led an investigator-initiated trial of targeting androgen receptor with enzalutamide in bladder cancer. Unfortunately, the trial was stopped early due to accrual issues.

After approximately 4 years at Moffitt, I joined the Masonic Cancer Center at the University of Minnesota in 2015 to develop and lead the phase 1 solid tumor program and lead GU research. I led trials like EV-103, Javelin Bladder 100, and SWOG 1216, as well as several first in-human trials, including the intratumoral trials with novel immunotherapy agents. I also led investigator-initiated trials like BLASST-1 of neoadjuvant gemcitabine-cisplatin and nivolumab in bladder cancer and investigating brentuximab vedotin in testicular cancer.

In 2019, I transitioned to the Cleveland Clinic to lead the bladder program, eventually becoming the director of the GU Oncology Program in 2021. I am also involved with translational research and have several federally funded grants, including Department of Defense (DoD) and R-01 grants. I have led trials like EV-302, PSMAddition, ENERGIZE, KEYNOTE-905, KEYNOTE-992, MORPHEUS, MAIN-CAV, and others.

My diverse experiences across different institutions have equipped me with valuable perspectives, enabling me to adapt quickly and effectively navigate various systems. It is truly gratifying to reflect on how my career has progressed despite some personal challenges and visa issues as an international medical school graduate.

You mentioned numerous clinical trials you have been involved in, both investigator-initiated and others. If you had to pinpoint, which trials had the most significant impact on patients with GU malignancies? What are the 2 or 3 trials of which you are most proud?

Dr. Gupta: The trials one develops from an original idea truly hold a special place. One such trial is the MAIN-CAV trial, an NCI phase 3 trial I am currently leading. MAIN-CAV underwent multiple conceptual iterations over the years, culminating in a novel approach of combining cabozantinib with maintenance avelumab, building on the success of previous trials like JAVELIN Bladder 100. I have also learned to embrace challenges. For example, the MAIN-CAV trial had to be closed recently due to the changing paradigm, but I still see it as a great learning experience and hope to generate good clinical and translational data in future.

Another trial I have led is the BLASST-1 study exploring immunotherapy and chemotherapy in the neoadjuvant setting before cystectomy We saw promising results and also were successful at obtaining a DoD grant for biomarker work.

My participation in the EV-103 trial examining enfortumab vedotin and pembrolizumab, where we put some of the first patients on this game-changing trial leading to the phase 3 EV-302 trial, which ushered in a new era of standard of care, was truly gratifying.

Each of these trials, regardless of their outcomes, has contributed invaluable insights that pave the way for future advancements in the field.

Could you shed some light on your role as the director of the GU Oncology Program at the Cleveland Clinic? What are your responsibilities? How do you balance patient care, research, and administrative duties?

Dr. Gupta: In my current capacity, I dedicate 2 full days to clinic and do some inpatient service.

With the help of my colleagues and an excellent research team, we have worked diligently to establish a comprehensive GU Oncology Program and have a well-rounded clinical trial portfolio across disease states like bladder, kidney, and prostate cancers.

We have cultivated strong collaborations in immunology and radiation oncology, bolstering our scientific endeavors.

Overall, my role is dynamic and exciting. I am thrilled to contribute to the advancement of GU oncology, both within our institution and on a broader scale.

Looking ahead, you have mentioned ongoing trials and the evolving landscape of GU care. In your view, what do you anticipate will be the most significant changes in GU care over the next 5 years?

Dr. Gupta: A key advancement we are hopeful for is the development of robust biomarkers to guide treatment selection. Currently, we lack reliable biomarkers at the point of care and often resort to blanket therapies like immunotherapy, which only prove effective in a fraction of patients.

Having biomarkers for efficacy and toxicity prediction would be transformative. It would spare patients the unnecessary physical, emotional, and financial burdens associated with ineffective treatments. Our ongoing work on the DoD grant in bladder cancer, where we study biomarkers of response and resistance to immunotherapy using cohorts like the BLASST-1 and PURE-01 trials and chemotherapy cohorts, will help advance our understanding of this topic.