BCAN session to highlight epigenetics and response to immunotherapy in bladder cancer

In this interview, Ania Woloszynska, PhD, highlights a session that she will co-chair at the Bladder Cancer Advocacy Network (BCAN) Think Tank titled, “Epigenetics and response to immunotherapy in bladder cancer – clinic to bench and back.” The BCAN Think Tank will be held from August 2–4, 2023 in Washington DC. Wolosyznska is an associate professor of oncology in the department of pharmacology and therapeutics at Roswell Park Comprehensive Cancer Center in Buffalo, New York.

Ania Woloszynska, PhD

You have a session at the BCAN Think Tank on epigenetics and response to immunotherapy in bladder cancer. What points do you expect to come up during this discussion?

First of all, I really hope it's going to be a vibrant discussion. Although it's a little bit difficult to anticipate what points are going to come up during this session, what I think is going to be important and what participants will be talking about is what's available in terms of basic science findings in regard to immunotherapies, as well as epigenetic agents. What are the data coming out of clinical trials using these agents? How can we critically evaluate that information in a way that will help us with future clinical trial design? In other words, how that information that comes from the lab and the information that comes from patients participating in clinical trials can inform the future of epigenetic therapy and immunotherapy for bladder cancer patients.

Could you touch on the potential of epigenetic agents such as EZH2, DNA methylation, and histone deacetylase inhibitors to affect patient response to immunotherapies?

There are a good amount of data from the basic science side, as well as the clinical side indicating that these 2 classes of drugs or these 2 types of therapies could potentially enhance one another. Moreso, epigenetic therapies enhancing the immune responses. Epigenetic drugs have been in the clinic, mostly for hematological malignancies, and that's specifically DNA methylation inhibitors. That's where the success mostly comes from. They have not been as successful in applying them to solid tumors, including bladder cancer. But they have this unique feature that allows modulation of the immune system, and there are data that supports that, data that comes from my laboratory as well as other laboratories.

One phenomenon previously reported in the past few years is called viral mimicry, which leads to immune responses that have the potential to enhance immunotherapies. We know that immunotherapy, although it has been very beneficial to some patients, not enough patients respond to, let's say, checkpoint inhibitors that we know have been approved for treatment of bladder cancer.

Another thing about these drugs is they can be used in patients at relatively low doses for a relatively long time with toxicities that are manageable for patients. So, combination therapies with those epigenetic drugs and immunotherapy have the potential of not being as toxic as some previous regimens and [may] allow patients who are often elderly with a lot of other health problems stay on these treatments and hopefully benefit from them.

What does the future look like for epigenetics in bladder cancer?

I think there's a lot of promise. I don't think we would have the session and this discussion if we didn't believe that epigenetic drugs have a place in bladder cancer treatment. So, I'm really optimistic that the session we are conducting will provide some recommendations [and] some ideas that will help us think about utilizing epigenetic therapies in a very evidence-based way and designing future clinical studies that will apply those precision personal medicine approaches where we will think about certain molecular characteristics of a tumor from a patient, and that will allow us to apply a specific therapy. That may be epigenetic therapy with immunotherapy.

Is there anything else you would like to add?

I think one thing that I would like to mention is how important it is what Bladder Cancer Advocacy Network is doing for this field. I believe this platform of putting together basic scientists, translational scientists, [and] physician scientists, is extremely important for any future success of this field. And by success, I mean trying to identify the best ways to design clinical trials for bladder cancer patients. So, I'm very grateful that we have this organization that allows this discussion and allows a conversation to happen. I'm excited to go and learn a lot and see this multi-level expertise that will be there and that will lead to incredibly robust conversations.