Daniel I. Simon, MD: Hello everyone. My name is Dr. Daniel Simon. I am your host of the Science at uh, podcast sponsored by the University Hospital's Research and Education Institute. This podcast series features university hospitals cutting edge research and innovations. Thank you for listening to another episode today. I am happy to be joined by our guests, Dr. Ted Technos and Dr. Gary Schwartz.

Welcome.

Gary Schwartz, MD: Good morning.

Theodoros Teknos, MD: Morning.

Daniel I. Simon, MD: Dr. Schwartz is a director of the Case Comprehensive Cancer Center and is a specialist in rare cancers like sarcoma. Dr. Technos is the president and scientific director for the University Hospital Seman Cancer Center at University Hospital's Cleveland Medical Center, and also serves as the Deputy Director of the CASE Comprehensive Cancer Center.

Clinically, Ted is a head and neck surgeon. I wanna start by congratulating both of you on securing your recent 25.5 million cancer Center support grant from the National Cancer Institute with a merit score placing the case Comprehensive Cancer Center in the top 4% of all NCI designated cancer centers nationally.

This renewal marks a 38 years of continuous funding of this center since its founding in 1987. Can you share with us how the center has evolved over these past decades? and what are your key initiatives, that are supported by the Case Comprehensive Cancer Center going forward in its first renewal?

Gary Schwartz, MD: Thank you, Dale. So I think we can sort of phrase it from single center to powerhouse consortium. we were founded as an NCI designated, cancer Center in 1987. eventually we achieved, we call Comprehensive Cancer Center status in 1998. Comprehensive means that we are able to engage the full spectrum of cancer research from bench top to bedside with effective engagement of our community partners, which is so critical for cancer Center, especially in northeast Ohio.

centered in Cleveland. In 2004, we expanded the center to include Cleveland Clinic. therefore, we're a consortium cancer center with two amazing hospitals, Cleveland Clinic, university Hospital, and also an exception university case, Western Reserve University. Our focus is on basic science across multiple disciplines, genetics, immunotherapeutics, the basic science of translational research and how to bring that, to the bedside.

it's basically has six critical programs, and our goal is to rapidly translate discoveries from the laboratory into the clinic and deliver them to the patients in northeast Ohio. And that's the way we vision it. And I think we've had great success. We have a great team, great leadership with Dr. Technos at University Hospital, and Dr. Ajay is the Cleveland Clinic, our clinical representation is exceptional and our science is, is exceptionally strong.

Daniel I. Simon, MD: So, Ted, you've been here now, I guess through two renewals, Tell me a little bit about your perspective of how you think. the next seven years of funding are gonna shape out compared to what you've had last.

Theodoros Teknos, MD: Well, I think, under Gary's leadership and prior to that, Dr. Stan Gerson's leadership, we were able to achieve extended funding. So instead of the typical five year renewal, we're able to get the seven year renewal due to the exceptional performance of the cancer center. So that brings some stability, to our funding.

this will also allow us to innovate and to create new programs. And I think, we will be stable with regards to our funding, but I think The investment of the individual institutions has increased dramatically. And again, as we look at, what the institutions are bringing in addition to what the Comprehensive Cancer Center Grant brings, it's really a remarkable amount of resources where we can expand our programs and really create even deeper fund of knowledge in the basic sciences as well as translational medicine.

Daniel I. Simon, MD: I guess I'm a little spoiled in the sense that in my career I've come from two consortium centers. the Dana-Farber with Mass General, the Brigham, and Beth Israel and Harvard Medical School, and now you come here and you have Case Western, the Cleveland Clinic and University Hospital. So it seems.

Natural to me to be in a, consortium allowing just amazing collaboration opportunities. But can you tell us a little bit, Gary, how do you as sort of the captain of the ship, navigate getting people to work together, in a common goal?

Gary Schwartz, MD: Well, I think cancer itself, Dan, is a unifying theme. I mean, everybody's been affected by cancer, either personally or by family, brother or sister, whatever it may be. So you mentioned that word and it resonates throughout all the consortium centers, and I think it's a unifying source. It's a matter where you sit.

We have a unified approach and how to. Tackle the cancer question. I think it brings people together in ways that are pretty special and it's reflected in of all of our, group meetings. We have an executive council that works closely with me that Ted and and others are involved with, and we meet every other week.

It represents. All the members of the consortium equal representation with University Hospital, Cleveland Clinic, and the university itself. And we discussed the issues that face our community. We've discussed the issues that are relevant to cancer research and how best to deliver those to the patients at Cleveland and the surrounding neighborhoods.

So it is a collaborative effort. We try to make sure everybody's voice is heard, and I think at the end of the day, we present a unified approach to cancer research and cancer medicine that's exceptional. High quality and results in amazing, opportunities and research both science and clinical for the patients in our neighborhoods.

Daniel I. Simon, MD: Ted, anything to add?

Theodoros Teknos, MD: I mean, I think leadership plays a big role. So I think, certainly Gary's leadership and, Dr. Gerson's leadership prior to that really are. Almost like Switzerland in terms of working between the organizations and, really it's a symbiotic relationship. You know, case is a tremendous basic science engine, but they don't have a hospital, so they really need to work with the hospitals to translate.

Their discoveries to patients. And likewise, our institutions really rely heavily on the basic science that's generated out of the labs that Dr. Gary, Dr. Schwartz oversees so that we can bring these new drugs to patients and differentiate ourselves as a region. Northeast Ohio from other parts of the country with these new discoveries.

So it really is very collaborative, but I think most importantly, it's the personal relationships. I think Dr. Schwartz, Dr. Aja and myself, are fully committed to eradicating cancer in this region, and we have great personal relationships which break down any institutional barriers that may exist.

Daniel I. Simon, MD: You know, for our patient listeners today, I think it's really important to emphasize that coming to a comprehensive cancer center. Is a great opportunity for you. we often cite that your survival from your cancer will be significantly improved by coming to a comprehensive cancer center. Can you explain to our patients why that's the case?

Why is it that when you come here, you're gonna do better?

Theodoros Teknos, MD: I think it's primarily Dan because of the level and the expertise of the individuals taking care of those patients. So I think, you know, there have been multiple studies and multiple. Disease types that show there is up to a 20% improvement in survival if you're treated at a comprehensive cancer center.

And that's because cancer is a team sport. It is very complicated. The support services that patients need, whether it be nutrition or social work or art therapy, music therapy, integrative, medicine becomes so increasingly important in the patient's overall survival. So the differentiator is. Really the expertise of the individuals, but then also the ability to participate in cutting edge diagnostics, therapeutics, and clinical trials.

Those are the things that allow patients to really get tomorrow's treatment today. And I think, that translates into better outcomes. And also I think the fact that we do multidisciplinary tumor board and really use the best evidence, and the latest signs to, to. Tailor patient's care really is what I think sets comprehensive cancer centers apart.

Gary Schwartz, MD: I would second that I've, been at two hospital systems, Columbia University, before that Memorial Zone Kettering, and I can say the integration of services at. University Hospital and our case, comprehensive Cancer Center is exceptional and extraordinary. I participate in tumor boards throughout the week. I do find time to see patients at a university hospital in sarcoma Monday afternoons.

and frankly, we have tumor boards that meet every week to discuss every single patient. And on their tumor boards, we have surgeons, pathologists, radiologists, radiotherapists, social workers. Everybody's integrated into a discussion about how best to manage the patient's care. And cancer care is complex and it's not one shoe fits all.

It's very, very complicated. Has to be seen from multiple perspectives and a university hospital in case Western Reserve. We offer those opportunities to our patients and that makes it unique. And we have the same things at at Cleveland Clinic I should add as well. So wherever we're seen in the consortium system, you offered a unique process that's really characteristic of, of a comprehensive cancer center.

And last point is what Ted was saying, clinical trials. It is an critical part that patients participate in clinical research. That is what makes our cancer center exceptional. We have over 300 clinical trials here at Case with involvement from both, uh, and Cleveland Clinic, and we encourage participation because only we're gonna advance cancer medicine through clinical trials.

It provides patients the latest advances in cancer medicine that are not ordinarily available in the community and what makes us really special and unique.

Daniel I. Simon, MD: Really great to hear, and I think, you know, we, we have this thing that we say all the time. Research is about hope. It's hope for patients, with limited options. And it's really getting that latest, you know, drug device or cell-based therapy that can make all the difference. And the only way to get it often years in advance of approval is through a clinical trial.

So one of the things I wanna shift gears to is. Treating cancer is really important. Preventing cancer could be even better. Or detecting cancer when it's at a very early stage, you know, would also be. So tell me a little bit about what is the cancer center doing, to prevent cancer, but also.

This, concept of early detection and using all sorts of new cell-free DNA blood tests, imaging modalities to get cancer early, and I know, Ted, this is something that's really important to you, and you have some really interesting data in your lung cancer screening program, which has been in the news lately.

Tell us a little bit about it.

Theodoros Teknos, MD: Sure. thanks for bringing this up because I think. It's critically important for anybody who's listening to realize that. It's intuitive, but it's really important that the earlier you catch a cancer, the more likely you're to cure it. Unfortunately, you know, many cancers are detected in later stages, stage three and four, and it's much, much more difficult to cure a cancer when you catch it in an advanced stage.

we've invested heavily in. Early cancer detection and also have created a diagnostic clinic for people who have suspicious lesions that could be a malignancy, so that we can work those patients up. An example that you alluded to is our lung cancer screening program. Cleveland has amongst the highest rate of smoking in the nation.

It was at one point as high as 33% in the recent years. Luckily, it's starting to come down significantly due a lot of the work that the cancer center is doing. But that's an incredibly high rate of smoking, and we had. Lung cancers that were being detected primarily at very late stages.

So we implemented a very robust lung cancer screening program. Only 7% of patients who are eligible for lung cancer screening actually get the low dose CT scans that they. they're eligible to receive. So we very aggressively, began screening patients who were at risk, started to identify them through their, electronic medical records, and have seen tripling of our, low dose CT screening for lung cancer.

And what we've seen is. That we now are detecting a much higher percentage, almost 20% higher rate of stage one and stage two lung cancers. And as a result, we really are improving lung cancer survival in northeast Ohio through these efforts. So that's one example of how. Lung cancer, I mean just cancer screening in general can save lives and especially as lung cancer is one of the deadliest cancers that we deal with.

And I know Gary through the cancer center is, doing remarkable work in prostate and others. And I'll let Gary comment on that.

Gary Schwartz, MD: Yeah. One of our true success stories, as Ted alluded, is been of prostate cancer. African American men have the highest rate of prostate cancer in the country. It's picked up late in the disease. It's more aggressive. So we had this idea, could we educate the barbers? what is a social center for black men in, in Cleveland?

And, it's the barbershop. So could we educate the barbers in Cleveland, how to have a discussion with our clients about the need for prostate cancer screening? So we started an educational course. We had 27 barbers participate in Cleveland. We taught them how to engage, not to cause fear, but to have a sense of trust.

We started running videos in the waiting rooms of all the barbershops about the importance of screening, and it featured African American men with prostate cancer, African American physicians, and the discussion began to take place. The goal was to encourage them to have a simple blood test called the PSAA prostate specific antigen, which when done can pick up prostate cancer in the earliest stages before it becomes advanced.

We started this, we screen now over 500 men in Cleveland, in the community. And we've actually picked up elevated blood tests with the detection of early prostate cancer that would not have ordinarily been suspected or anticipated by routine examination. It was only the blood test itself that picked it up.

And these patients were then referred to uh, for the necessary and excellent care they received that ultimately cured them of their cancer. So here we are taking a simple test, educating the community, informing them, and directing them to the optimal care to save lives. What can you say more about a comprehensive cancer center, Dan, than that?

Daniel I. Simon, MD: Yeah, that's really, a great story and a perfect segue to my next question. So here we are. it's a biomedical mecca in Cleveland. We're so fortunate to have two top. Top 10 academic medical centers by UK brand Finance, in the US and two top 20 in the world. So we've got the horsepower.

The problem is we have amongst the highest cancer mortality rates. And so that tells you that, you know, we have some problems, especially in Cleveland and Cuyahoga County. Where there's a, concern that obviously social determinants of health, poverty, air quality, walkability, temperature variety of things, are related healthcare access are related to cancer outcomes.

I know, Gary, that this is a central component. Of what you're trying to do with community in this grant renewal. So can you tell us a little bit about what are you doing to tackle this disparity in cancer outcomes in Cleveland and our surrounding counties?

Gary Schwartz, MD: So we have an exceptionally strong, population cancer analytic program, and we track all the incidents of cancer, both in Central Cleveland and the surrounding counties, and identified hotspots where cancer is emerging. For example, we discovered that melanoma we. Is exceptionally high in Cleveland and the surrounding counties. Now we're not sure and we can have all sorts of hypotheses why this may be the case, especially 'cause we're cloudy most of the year.

I mean, think someone said we have only 66 days of sunshine a year. I, that seems a little low to me, but that's what this districts show. being that sad, how do we. Skin cancer. Well, simple. It's prevention, it's use of sunscreen. So this summer we actually went out and put kiosks in all the county pools and parks and provided free sunscreen with the collaboration of L'Oreal Poe to all the Cleveland and surrounding county communities.

So wherever you were in Cleveland or the 15th surrounding counties out to Lorraine, there was a kiosk with sunscreen for cancer prevention. On those kiosks, there were QR codes, which allowed people to be educated, brought them right to the cancer center. And also we asked interesting and important questions like, do you know the sunshine causes cancer?

Do you know the sunburn cause of cancer? And unfortunately, there are people that do not know those associations. So we have a lot of work to do in our community to not just prevent, but to educate as well. And I think the sunscreen program is one good example. I can give others, but I'll, hand it over to Ted, and pick it up from there.

But I think it's just what we can do, what we can achieve, and hopefully this will impact and prevent cancer. 'cause frankly, it's a lot better and cheaper and more cost effective to prevent a cancer than to treat it.

Theodoros Teknos, MD: Absolutely. Yeah. Thanks Gary. And I think part of our initiative as a comprehensive cancer center, and this is a requirement. By the federal government as part of our funding is for us to actually sit down as a cancer program and analyze these disparities and come up with key cancers that we are addressing in our community.

So, you know, it's really called community impact and. the NCI requires us to actually focus on those cancers that are most prevalent in our communities. And I think, strategically we actually come up with initiatives to address those cancers. So, Gary mentioned melanoma. there are other key cancers that we've really identified and, and I think one that Gary has really identified recently is, multiple Myeloma is a major.

Problem amongst African Americans, esophageal cancer is at much higher rates here than other parts of the nation. So we have initiatives to address those because those impact our catchment area. And we strategically provide and create programs to address these disparities that are present in our community lung cancer too.

So that's why our lung cancer screening program is so important.

Gary Schwartz, MD: It even extends beyond that. for esophagus cancer, we've actually developed a tool that a generalist can use in their office to detect early onset esophagus cancer and pick it up before it actually becomes esophagus cancer. That's a tool that established at, uh, case Western Reserve. It is an amazing tool.

That is now we think saving lives. And, it was all discovery made here by researchers and, at case. and I put in the clinical practice and being evaluated still in some of our programs. So, it does require technology as well to, pick up these early stage diseases. Dan mentioned circulating DNA and those types of approaches.

So we're at the forefront of all these, and it takes the hospital partners to make these possible.

Daniel I. Simon, MD: Yeah, I think it's great. You know, we have featured, Sandy Markowitz and Amato Cho and Joe Willis before about ESO check and ESO guard, which is that Swallow the Balloon and pull it back. as you mentioned, special populations we're so proud of our work with the uh, emergency. medicine, institute, which is our EMS team, going to firefighters who are at high risk from occupational exposure and we offer that test as part of cancer screening, for them.

So that's really great. Well, I wanna ask each of you a question about your own cancer area of interest, so you can give us an example of what's new and on the horizon. So, Ted. You are a head and neck cancer specialist. I guess as you've and I have talked a lot, it's all about HPV and the high rates of human papillomavirus, positive head and neck cancers.

Tell me a little bit about how the, the treatment is changing and how your own lab has new therapeutics, in this head and neck cancer space.

Theodoros Teknos, MD: Yeah. Thank you Dan. So it's really not well understood in the general public, but HPV causes now the majority of head and neck cancers in the United States. when all of us were training, it was all about smoking and alcohol use and that still plays a very, very important role.

But human papillomavirus infection now is causing. An overwhelming number of cancers that arise in what's called the oropharynx. That's the tonsils and the base of tongue. When you look. Over the last 30 years, the incidence of these cancers has increased by 300%, which is really remarkable. And it's primarily in those individuals who have never smoked and never drank, and it's HPV infection that they incurred during their, teenage and early 20 years.

Fortunately, the HPV vaccine is totally protective, for many of these strains that cause the malignancy. But there are literally millions of men and women in the country, primarily men. It's three to one, a male to female disease, but who have this infection that they haven't cleared. The overwhelming majority of people clear these infections, but there is a pool and a prevalence of people who carry oncogenic HPV infection in their oropharynx.

And over time, the longer people live, the more likely they are to develop one of these malignancies. So here at uh, and Case Western, we have intensive research focused on how do we A, prevent those individuals who are carrying the virus from developing a malignancy? And then B, once they develop it, what's the best way to treat it?

Because these treatments can be very toxic. They can a lot of. Swallowing problems and other issues related to their chemo and radiation therapy treatments. So it's really a multi-pronged approach. How do we treat those patients more effectively and with less toxicity who have this disease? Luckily it's incredibly curable, but you know, we need to cure them with less toxicities and how do we prevent them from going forward?

So with that said, you know, the work in. Primarily Dr. Quentin Pan's laboratory has identified the mechanisms by which HPV causes malignancy and actually has developed inhibitors to reverse and reactivate, the guardian of the genome, P 53 HPV, and activates P 53. And by this medication, this drug that's been developed.

We can reactivate P 53 and these tumors shrink and go away with very minimal toxicity. We're actually curing these in the lab and. You know, as it happens with drug development, a company licensed this drug so that we could bring it to the clinic, but that company went out of business during COVID, so we were left with a dilemma.

how do we, take this very promising technology to patients? So we did a drug screen and actually found a drug that's been used for 30 years that does this exact same thing. it's called Fenofibrate. It's a cholesterol drug and it reactivates P 53 and HPV positive malignancy. So we now launched a clinical trial using a, long known well tolerated drug in cervical and head and neck cancer.

And we're seeing P 53 reactivation and actually, you know, regressions of these tumors, using a drug that is very, very low toxicity. So that's an example of how you learn the epidemiology. You learn how a, you know, a virus causes cancer. You create a drug, but then you get creative to bring it to the bedside and actually, enact some real meaningful change in your community.

Daniel I. Simon, MD: That's great and so. you treat some tough cancers, sarcomas, osteosarcomas, a rare cancer, very difficult adolescent, young adult population, you know, also affected. what's changing in sarcoma?

Gary Schwartz, MD: Yeah, you're right Dennis. It's a complicated, and, when it's an advanced setting, there are minimal therapeutic options for these patients and as a disease of the connective tissue or the bone, and it affects both children, young adults, and older patients as well. So one of the issues we've been working on, there are two approaches how to make immunotherapy effective, which has been a challenge.

Unlike recent advances had neck cancer where immunotherapy will play a role. We're still trying to figure this out in sarcoma, based on my own lab data. Actually, we just finished a clinical study showing if you use a drug used in breast cancer called palbociclib, that if when combined with immunotherapy, it greatly enhances the effects of immunotherapy.

Palbociclib was a drug used in a sarcoma subtype called Lipos sarcoma. We just completed a randomized clinical trial comparing this breast cancer drug now being used in these sarcomas in combination with immunotherapy. It was a national study and we're waiting for the results and we're, we hopefully will make them available before the next national cancer meeting.

My personal focus now on more the adolescent child cancer in particular, A disease called Ewing sarcoma. It's a disease that starts in bone. We see it in young adults and children, and when it metastasizes, chemotherapy can work, but often there are failures. So it's caused by a protein, is called EW sly one.

And this is a fusion. What is a fusion fusions? We, we take two proteins and make one. And we see this a lot in sarcoma, and it's been undruggable. There've been, I can't tell how many gazillion of dollar has been invested in trying to find how to drug these fusions.

Best. You just fly one. So in my laboratory, we've been working on, on trying to block the production of the protein that we call the RNA level. DNA goes to RNA goes to protein, so we've been working on how to prevent the RNA formation of of that eventual protein and have actually identified a drug.

We're actually working with a small biotech company that suppresses the expression completely. We've worked at the mechanism. And we've given it to mice. I guess that's always the first part. You gotta start someplace. And we're actually having a profound effect on causing other tumors to respond. And based on this data, we will soon be launching a national clinical trial starting here at case with, uh, being the primary site testing a drug called Citroens.

It'll be the first R class who we think effectively inhibit the expression of Sly one. It's been reviewed by the NCI. It's been granted accelerated status. It's gonna be a national trial because it's a rare disease and takes many centers to participate, but University Hospital and the case center will be the lead site for the whole country.

And we anticipate starting this trial at, uh, in Cleveland at case in the next six to 12 months. I've never been so hopeful in my, in my life, Dan. I've been working in this field for 25 years and I think I finally have a drug that'll really have an impact on a rare cancer.

And the great thing is all the resources done here at Case. On a laboratory in this building, and we're gonna take take it it from the lab to the clinic to patients. We started this a year and a half ago, rapid translation. that's what the Case Comprehensive Cancer Center can do.

When you say, what do we do? This is what we do. We bring discoveries in our laboratories and bring them rapidly to the patients. So it is this type of approach for sarcoma that does give us hope. And that's what we have to look into, the hope for the future, that our researchers can make these type of discoveries and have an impactful, impact on the cancer and the families and everybody associated with these diseases.

Daniel I. Simon, MD: Wow. Well, that's such an inspiring, story, Gary, and we wish you luck and we'll invite you back to report on those results. I wanna thank both of you, Dr. Technos, Dr. Schwartz, for taking the time to speak with us, today. To learn more about research at University Hospitals, please visit uh hospitals.org/uh, research.

Thanks Gary and Ted.

Gary Schwartz, MD: Thank you.