Jonathan Coleman, MD – Pioneering New Understandings of Upper Tract Urothelial Carcinoma

By Jonathan Coleman, MD, Zachary Bessette - Last Updated: February 7, 2023

Jonathan A. Coleman, MD, is an attending surgeon and urology specialist at Memorial Sloan Kettering Cancer Center, as well as a Professor of Urology at Weill Cornell Medical of Cornell University. He has been a faculty member at Memorial Sloan Kettering since 2006. His research endeavors have been paramount to the current understanding of upper tract urothelial carcinoma (UTUC).

GU Oncology Now spoke with Dr. Coleman regarding his unique career path, his role in helping define UTUC as a unique disease, and ongoing research to improve patient outcomes in this setting.

Why did you become a urology specialist and surgeon? What was your inspiration?

Dr. Coleman: My inspiration for entering the field of urology occurred during medical school. I came in contact with the Chairman of Urology at Cornell University Medical College: Dr. Darracott Vaughan. It was the most casual encounter, but it was life-changing for me. At the time, I was planning to pursue a career in cardiothoracic surgery, I had applied to programs, and was in the process of arranging interviews. One day, I was in the operating room helping on a case with the Chairman of Surgery, who was performing a liver resection, when Dr. Vaughan came in to perform an adrenalectomy for an adrenal tumor that was discovered. I asked if I could stay and watch him perform the operation which he agreed, and during the surgery the teaching experience and discussion was unlike any conversation I’d had before in the operating room. He described the details of adrenal cancers, the physical manifestations, medical work-up, and endocrine studies to perform. He described the details of adrenal surgery, vascular anatomy, and demonstrated surgical techniques that were masterful. He also wanted to know more about me, what I was doing, what my plans were, and any research I’d done. In short, he sparked an interest in a way that great teachers and mentors have a unique way of creating. After the case, he invited me to his office and we talked more about urology, which was a specialty I had never contemplated prior to that time, and that was the moment I decided to look more closely at urology.

The field of urology has so much to offer. As a surgical specialty, it has great breadth in care over a patient’s lifetime and we often develop long-term relationships with our patients. The medical work-up and evaluation of diseases that affect the urinary system can be challenging and complex which makes it an interesting and academic specialty. Clinical and translational research opportunities are outstanding. Furthermore, the therapeutic interventions are diverse, including medical treatments, endoscopic, laparoscopic, and open techniques that are highly technical and also very effective. Being able to offer our patients curative therapies that are typically well tolerated can make them very happy with their outcomes. All of this can lead to a satisfying doctor-patient relationship which is one of the reasons many of us enter the medical profession: to help people get better.

In your time at Memorial Sloan Kettering, what has been your most meaningful or impactful contributions to the field of urology?

Dr. Coleman: I enjoy working in academic medicine and working at a place like Memorial Sloan Kettering offers opportunities to work with outstanding colleagues and leaders in oncology to investigate important questions. I really enjoy teaching and the fellows we train here at Memorial Sloan Kettering are among the most outstanding young minds in medicine. My mantra has been that in order for the process of medical education to be effective and progress to be made, the next generation of physicians has to be better trained than the generation before. When interacting with and training our fellows, my goal is to help them be better surgeons and academicians than my peers and me. So that’s a main motivator for me as an educator and mentor.

As for my basic science contributions, I’m most proud of the work our laboratory research team has done investigating UTUC, which is regarded as a distant cousin to bladder cancer. Through some of our investigations, we’ve been able to show that biologically and genetically, UTUC differs significantly from urothelial cancer of the bladder. Helping to define UTUC as a unique disease within urologic oncology has been an important endeavor as we look for better therapies to develop as a result of this research. From a clinical research perspective, we’ve also run several clinical trials in UTUC that we feel is helping to provide better treatment options and outcomes for our patients. We’ve just published our results of a completed trial for neoadjuvant gemcitabine cisplatin that supports the role for platinum-based chemotherapy prior to surgery as a standard-of-care option for managing patients with high-risk forms of this disease.

The Jonathan Coleman Lab is a dedicated space for you to research the mechanism of disease recurrence, response to therapies, and disease progression of UTUC. How did the Laboratory come into being?

Dr. Coleman: In academic medicine, it’s rare to find a place that offers the resources to support basic science medicine and translational medicine at a high level across the board. There are some centers that do it, but here at Memorial Sloan Kettering, not only do we have access to world-class labs, we also have world-class collaborators – basic scientists and physicians working closely together who are devoted to studying oncology to improve care as quickly as we can. When I walk the hallways, I have the opportunity to interact with colleagues who are leaders in their field and also researching and treating some of the most challenging malignancies. This environment becomes a sort of incubator of thought, and the cross-fertilization and collaboration that can occur in unique environments like Memorial Sloan Kettering is incredibly important for making advances in cancer care. It takes personal proximity and interaction to make that happen organically.

I was brought here to focus on the treatment of malignancies that involve the upper urinary tract, which includes kidney cancer, renal pelvis cancer, and adrenal carcinomas. It didn’t take long to see that UTUC was an understudied field, one that was related to bladder cancer but had not been thoroughly investigated and lacked defined clinical paradigms for management. I was able to team up with several excellent researchers and clinicians, including Drs. David Solit and Dean Bajorin, to examine UTUC as a unique disease. I was very fortunate to receive funding from a variety of sources, including grants from the Thompson Family Foundation and Department of Defense, to develop our research interests in upper tract cancers, and specifically to develop novel types of therapies for treating UTUC.

Which of your current research endeavors are you most excited about?

Dr. Coleman: We’re investigating a form of therapy called vascular targeted photodynamic therapy, which utilizes an agent called WST11. It was developed as an anti-cancer therapy by Professors Avigdor Scherz and Yoram Salomon at the Weizmann Institute of Science in Israel. The story is an interesting one: Dr. Scherz’s wife developed an aggressive form of breast cancer, and as a plant scientist, he wanted to know if there was anything that he could do to come up with a new therapy for her. He turned to his understanding of plant biology and began studying how plants could defend against pathogens. He found that plants use a special type of chlorophyl to combat pathogens and he was able to purify and modify a form of chlorophyl to use safely in humans. The chlorophyl-based agent is given intravenously and then activated by light inside the body to serve as a targeted photodynamic or photo-chemotherapeutic drug.

While WST11 was initially developed for treating breast cancer, it went on to be tested successfully in prostate cancer, including in clinical trials that we ran here at Memorial Sloan Kettering. We saw the potential of this agent in a variety of cancers and began working in the lab to look at its utility in UTUC. We were able to translate our results into a phase 1 trial completed last year that demonstrated early safety and efficacy in patients with UTUC while also preserving the kidney. Organ-sparing management is a key priority in cancer care, allowing us to provide patients with a curative outcome with the least detriment to quality of life. We want patients to live normal lives without dealing with the devastation of, say, removing a kidney, which may risk the need for dialysis. To this end, developing photodynamic therapy for UTUC is a worthy endeavor, and we’re thrilled to continue our work with the multicenter phase 3 ENLIGHTED trial which recently opened at centers throughout the US and some international sites.

How do you envision the urologic cancer treatment landscape advancing within the next 5 to 10 years?

Dr. Coleman: Cancer care is always seeking to improve and constantly grapples with questions of how to improve upon established forms of care, optimize delivery, and look to the future to improve treatment with new therapies. We are in an era now of unlocking some doors, through genomic and tumor microenvironment studies, to better understand the biology of cancers and how to better target tumors with fewer side effects – a form of personalized medicine. We are already seeing some incredible successes in a few very specific forms of cancer which, along with less invasive forms of surgery, allow for better organ-sparing strategies. So, I believe for the next 5 to 10 years, we will see more refined treatments with better risk-stratification and selective therapies being applied to offer more effective forms of treatment to patients while avoiding some harms that can come from over-treatment.