Melanie Cole (Host):  Molecular markers offer increased opportunities to improve understanding of the biology and treatment of bladder cancer.  My guest today is Dr. Joshua Meeks.  He’s an assistant professor of urology, biochemistry, and molecular genetics at Northwestern Medicine.  Dr. Meeks, what a pleasure to have you on with us today.  Tell us a little bit about Northwestern Medicine’s approach to treating patients with bladder cancer.  How is it unique?

 

Joshua Meeks MD, PhD (Guest):  One of the unique features that we offer for patients is that really, we cover the entire spectrum of bladder cancer and urothelial carcinoma.  From top to bottom, from early stage to advanced stage disease, and really, I’d say that the unique features that we offer—number one is a multidisciplinary approach to this cancer.  As it (0:55) becomes more aggressive, we certainly have a lot of opportunities for patients to see patients in medical oncology, radiation oncology, and surgeons like myself in urology.  Second, we have multiple clinical trials open across the spectrum of bladder cancer and urothelial carcinoma so that patients who, you know, a lot of folks don’t necessarily know how to manage at other hospitals, we see them here routinely.  We have many opportunities for them to both get involved in research and also offer opportunities for treatment of their cancer.  

I think from the third end is really because we’re built on the foundation of the university, and we have collaborators across the university in the basic science departments and translational research is that much of what we do goes towards basic research here.  That really goes from patient care from the bedside directly to the bench and then that fuels the next generation of discovery, which then goes back and then helps the patients that we’re taking care of.  I mean, just in my short time of being here, I’ve seen patients cured, treated, offered new approaches that simply weren’t available, even just a few years ago.  So, I think that really shows sort of the dynamic range of what we offer to patients.

Host:  Really?  What an exciting time to be in this field.  So, Dr. Meeks, you’re currently researching the underlying genetics of and epigenetic changes in bladder cancer to develop new treatments for the disease.  Share some of your findings or results with us If you would.

 

Dr. Meeks:  You know, when we look at this cancer, which is the fourth most common cancer in men, the sixth most common cancer overall, that one of the challenges of this cancer is that, you know, once it becomes metastatic, once it leaves the bladder and goes elsewhere, our survival is very low.  It’s the second worse survival overall just behind lung cancer, and so it’s a pretty aggressive tumor, and we face that challenge with many of our patients, and so one of the things that my laboratory really tries to study is—can we look at the basic biology of these tumors?  Of the genes that have mutations in these cancers and how they change, can we use those mutations to treat the cancer—to really attack those vulnerabilities that are specific for that.  One of the things about bladder cancer that’s unique is that it has a number of mutations in genes that kind of are involved in how the DNA is wrapped.  That’s very unique for bladder cancer, and there’s actually very interesting therapies that are based on that.  

So, we have clinical trials now, where we—based on our research that we can give those patients these drugs—even combine them with immunotherapy to attack the tumor from multiple approaches, and so, we really think that that kind of strategy of attacking the tumor from multiple fronts:  one, using immunotherapy and then combining it with a very precision target will ultimately help patients and improve their survival.

 

 

Host:  Then expand a little bit more on that, Dr. Meeks.  Talk about the immuno-oncology in bladder cancer and how manipulation of immune checkpoints could improve patient outcomes.

 

Dr. Meeks:  Bladder cancer is one of the few cancers that is very immunologically active, and so when you look across tumors, the tumors that tend to be caused by carcinogens such as lung cancer, melanoma, and then bladder cancer tend to be more active and responsive to immunotherapy.  We know that at the more aggressive end, bladder cancer has about a 25-30% overall response rate to checkpoint therapy.  On the early stage, we use tuberculosis or BCG as an immune stimulant in the bladder, and by and large, I’d say in the neighborhood of 70-80% of patients at least have some response to that therapy, and all of that is because of the biology of these tumors that they tend to have enough immune activating properties that If you stimulate the immune system—not only does that cause improvement in response to cancer killing, but it actually, for some people, can lead to a durable cure.  The challenge though is that—the other side of the coin—is that there are people who don’t respond or they just—they’re not able to get that immune activation.  So, one question that we’re trying to really address is how do you take a tumor that shouldn’t respond or doesn’t respond and maybe make it responsive.  That’s where we think potentially combining therapies may ultimately improve the outcomes for many patients.

 

Host:  That’s so interesting, Dr. Meeks.  So, what do you see are some of the challenges of marker introduction into clinical practice?

 

Dr. Meeks:  The biggest challenge that we have with this cancer is that across the board, there’s a lot of variability in the tumor, and you know, we’re able to study cancers at the single cell layer.  So, for example, we can collect a tumor from the operating room and look at, you know, 10 to 15 thousand individual cells, look at the top 50,000 genes expressed in that one cell, and that—we’re trying to look at that information and then see how to better treat a patient.  So, I guess one of the concerns I have is we can study individual patients very well, but then how do we put all that together because across the board, bladder cancer tends to be very heterogeneous, meaning that there’s different responses among different patients, and so there’s not going to be a one-size-fit-all approach for patients and for their cancer.  I think we’re going to need multiple different therapies.  So, for now, to look at biomarkers and how we use them, I think it’s really trying to figure out what are the right biomarkers, what are the right therapies that can ultimately be applied to individual patients, and so, you know, we really use this question of, you know, going from the bedside to the bench to really understand people’s cancer better because I really, again, feel that that’s really going to help us long term—treat them better and treat their cancers.

 

Host:  Speaking of long-term, Dr. Meeks, where do you see this going in the next 10 years as far as patient outcomes and diagnostic accuracy and surveillance?

 

Dr. Meeks:  The further we get down this road of precision oncology, the more we’re going to know about patients and their tumors and how they respond.  My own sense is that, you know, very soon we’ll be profiling everybody’s tumor and profiling their blood to know what’s the best drug for their tumor and then what’s the best therapy that will work in their body.  So, I only see precision oncology going further and further, and I think, once again, my hope is that long-term that will lead to better outcomes for our patients.

Host:  As we wrap up, Dr. Meeks, what else would you like providers to know about optimizing effective treatment and bladder health among patients with bladder cancer?

Dr. Meeks:  One of the benefits of being at an institution like this is that we’re able to just focus on these very challenging problems.  I know that many of our providers don’t see these kinds of cancers very commonly, and then there’s some of us who are able to focus on this.  For example, that’s all I really see here at Northwestern.  So, for all of our collaborators, all of our people in Chicago that we work with, we get a number of calls just even asking questions about what’s the best answer.  You know, our phones are always open; our doors are always open to either see patients or even just talk to  the providers about what’s the best next step for patients out there.

Host:  Thank you so much, Dr. Meeks, for joining us.  What a fascinating topic and the work that you’re doing.  That wraps up this episode of Better Edge, a Northwestern Medicine podcast for physicians.  To refer your patient to Northwestern Medicine or for more information on the latest advances in medicine, please check out nm.org to get connected with one of our providers.  If you found this podcast informative, please share on your social media.  Share with other providers and be sure not to miss all the other fascinating podcasts in our library.   Until next time, I’m Melanie Cole.