Expert Stresses the Importance of More Precise Treatment of Kidney Cancer

Sunil Sudarshan

Immunotherapy and targeted therapies for the treatment of kidney cancer have advanced the field in recent years, according to Sunil Sudarshan, MD. This is particularly true for patients with advanced kidney cancer.

As the treatment landscape continues to evolve, there are additional precision medicine opportunities that investigators have yet to explore, said Sudarshan, professor, Department of Urology, Heersink School of Medicine, University of Alabama. One potential advancement is the introduction of new immune checkpoint inhibitors. Also, Sudarshan sees the potential to target the epigenome in patients with kidney cancer.

In an interview with Targeted Oncology™ following the International Kidney Cancer Symposium 2021, Sudarshan, discussed the kidney cancer paradigm and opportunities to advance the field with new targets.

TARGETED ONCOLOGY ™: What is currently in oncologists’ toolbox for kidney cancer treatment?

Sudarshan: I would say that the landscape of kidney cancer, particularly for advanced diseases has dramatically changed since my training. That was when targeted therapies were first introduce in the field. My personal outlook on how patients with advanced kidney cancer fare has really changed. It has become far more optimistic. Largely, that's probably because of advances in immunotherapy. I think that's really been the game changer over the last few years.

At the same time, we have a lot of gaps. During IKCS 2021, there was a presentation given by James P. Allison, PhD, in which he alluded to some of those gaps, which include, the fact that not all patients respond. A significant proportion of patients do not have durable responses, even if they do have an initial response. And we really don't know what those factors are that are contributing to sensitivity or response. I think we need to focus on trying to elucidate those factors, to really try to enhance therapies for patients.

Another important thing is the lack of robust models to test some of these hypotheses out. I think that's something that we really need to work on trying to develop and get out. So, some of the efforts that the Kidney Cancer Association has funded and tried to support in terms of developing SIND genetic models are relevant models of kidney cancer, that are immune competent. I'm very hopeful that these efforts can lead to accelerating those discoveries.

With clinical research in mind, what are the key research topic in renal cell carcinoma (RCC) right now?

I think we're really trying to find out what are the best rational combinations and sequences of therapy. So, some of the more whole genome wide approaches are hopefully going to yield some new insights in terms of immunotherapies, because I think that there are some of the approved checkpoint therapies. But as we heard during IKCS 2021 some of the keynote addresses, there are other immune checkpoints that are worth investigating. So, I think that investigating some of those other checkpoints, and whether they could perhaps synergize with the currently approved therapies is a real opportunity.

What other unmet needs do you think are important to highlight?

Being from the South and practicing in a population that is heavily African American, I think that there are a lot of disparities that are worth noting. And really, we need to delve in them. For example, if you look the very initial level of histology, the histological makeup for African Americans is very different from Caucasians. Another very clear example is the incidence of VHL mutations in African Americans with renal cancer is very different from Caucasian. So, I think that we need to really know that there are these disparities that exist, and that there are opportunities to shed light on new biologies, as well as improve therapies in a far more focused manner as we uncover these differences and what their biological significance are.

What excites you about the future of kidney cancer treatment?

I'm excited about some of the metabolic insights that are coming out about kidney cancer, with regards to glucose oxidation, including the metabolism I think those have been. Those are some of the groundbreaking studies. And I think what I've really come away is knowledge about the coordinated level of effort it takes amongst the basic researchers, the translational researchers, clinicians, and clinical research infrastructure to make those things happen in a very coordinated and seamless manner. We see the end product, and we really don't see what all it took to get to that point. So, I think that there's really been an appreciation for a lot of those layers that maybe don't come out in the final product. Also, those individuals that really contribute to that process have really laid out a roadmap for many of us who are interested in various aspects of metabolism or basic biology and tried to maybe incorporate some of these patient-driven models into our own research programs.

Regarding immunotherapy, I think we’re all really excited about immunotherapy. But there are other opportunities out these. Kidney cancer is prime for agents that perhaps target the epigenome. Maybe those can also interact with immunotherapy. I think overall, there's some opportunities there that we need to explore, cultivate, and provide opportunities for investigators who are looking at those.