In this episode of “Plugged in to Public Health”, Lauren speaks with Dr. Jill Kolesar about ovarian cancer, precision medicine, and the challenges of translating scientific discovery into real-world care.

The views and opinions expressed in this podcast are solely those of the student hosts, guests, and contributors, and do not necessarily reflect the views or opinions of the University of Iowa or the College of Public Health.

Lauren Lavin:

Hello everybody and welcome back to Plugged in to Public Health. Today’s episode explores precision medicine, cancer research, and how scientific discoveries move from the lab bench to real patients. I’m Lauren Lavin. I’m joined today by Dr. Kolesar, a pharmacist and cancer researcher whose work focuses on ovarian cancer, molecular tumor boards and innovative cell-based therapies designed to make resistant tumors responsive to treatment. In this conversation, we discuss how a PBS documentary about tumor-infiltrating lymphocytes shaped her career path, why ovarian cancer remains one of the most difficult cancers to treat, and how researchers are working to heat up tumors that traditionally do not respond to immunotherapy.

We also explore the role of molecular tumor boards in explaining access to precision medicine, particularly for rural and community oncology practices. If it’s your first time with this, welcome, we’re a student-run podcast that talks about major issues in public health and how they’re relevant to anyone, both in and outside the field of public health. So let’s get Plugged In to Public Health. Plugged In to Public Health is produced and edited by the students of the University of Iowa College of Public Health. And the views and opinions expressed in this podcast are solely those of the student hosts, guests, and contributors. They do not necessarily reflect the views or opinions of the University of Iowa or the College of Public Health. Well, thank you Dr. Kolesar for being on the podcast today. I’m really grateful that you took time out of your busy schedule to chat with us. So could you start by sharing a little bit about yourself, your path into pharmacy, and then eventually what drew you into cancer research and precision medicine?

Jill Kolesar:

Sure, and thank you very much for having me on the podcast, Lauren. Well, where I started out, I’m from Orienta, Northern Wisconsin. I’m a first-generation college student. And when I went to the University of Wisconsin as a bright shiny freshman, I hadn’t had the benefit of a guidance counselor. So when I picked my major, I just picked my favorite class, which was chemistry. So then I get into chemistry and I still like chemistry, but it was not clear what the job path was. One of the job paths was to be a high school chemistry teacher. So I was trying to think by the time I get to be a junior, you start thinking about what am I going to do when I’m done? And so I happened to have a work-study job in the physics department, and to get there, I had to walk through the College of Pharmacy. There was a bunch of brochures sitting out saying, “Hey, would you like to be a pharmacist?”

I mean, at that point I probably hadn’t even heard of pharmacy. And I mean, I’d heard of pharmacies, but I didn’t know that the career path we have a pharmacist at all. And so I picked up the brochure and looked at the back and I had all the prerequisites. So I applied to pharmacy school and the rest was history. I got in. And how I got into cancer is, it’s a funny story. I was in my second year of pharmacy school and I saw a program on PBS and it was about TIL therapy, which is tumor-infiltrating lymphocytes. And I have to say that this was probably 30 years ago, and I saw this show and I was like, “Oh, that is it for me. I am going into cancer research.” Because I just thought it was so cool. They’re like lymphocytes that seek into the cancers and are able to target the cancer specifically and to kill the cancer cells. And so I just thought that was fascinating and decided I was going into cancer research that day. And also I have never regretted that decision.

Lauren Lavin:

I love how your story just maybe reminds students that it doesn’t have to be that deep. Sometimes when we’re making these big decisions, we sit there and agonize and it sounds like it was kind of eureka moments and you were like, “Yep, this is what I’m going to do.” And then you just go out and do it.

Jill Kolesar:

It is. I was so fascinated by that and I remain fascinated by it today. And interesting side note, the tumor-infiltrating lymphocytes were approved two years ago for melanoma, so.

Lauren Lavin:

You were way ahead of your time. And where did you do your undergrad and then pharmacy school?

Jill Kolesar:

I did three years of undergrad at the University of Wisconsin, and then I went into pharmacy school there. At the time, it was a five-year degree, and so I have a BS in pharmacy, and then I went to the University of Texas Health Science Center for a post BS PharmD, and I stayed there for a residency and a fellowship.

Lauren Lavin:

Okay. So you’ve been around in the Midwest. So you also specifically focus on ovarian cancer. What motivated you to focus on that and why is that such a difficult disease to treat?

Jill Kolesar:

Yeah, ovarian cancer, we haven’t had any new treatments for ovarian cancer that have made a big difference. I mean, we’re still treating ovarian cancer essentially the way we were treating it in the ’60s with a platinum doublet.

Lauren Lavin:

Sorry. Why do you think that is?

Jill Kolesar:

Well, that’s a hard question to answer, but the two major advances in cancer therapy over the last few years, the first one is immunotherapy. And immunotherapy just doesn’t work for ovarian cancer. And the reason it doesn’t work is because the ovarian cancer is made up of these M2 macrophages, which basically make a little warm cozy space for the cancer to grow, and they feed it. And so when you have that kind of a tumor microenvironment, immunotherapy is essentially ineffective. So that’s one reason. And the other big advance are now we know if you have a specific mutation in your tumor, a lot of times you can develop a drug that targets it specifically. And so they’re great because you only have the mutation in the cancer, and so it attacks the cancer cells or can kill the cancer cells, but leaves the other ones alone.

And we haven’t found that many targets yet in ovarian cancer. So that’s part of the problem. And I think a third really big problem is they’re usually diagnosed at late stage. There’s not a lot of symptoms in early stages, and so most people are diagnosed at stage four, which is the worst or most advanced. And so when you take those things together, I think that’s what makes ovarian cancer a very tough cancer to treat. And the other thing is about 80% of patients will die of their ovarian cancer diagnosis within the first five years. So just a huge unmet need, and that’s what really motivated us to work in that space.

Lauren Lavin:

What are the symptoms that people do recognize that prompts them to go get treatment for something like this?

Jill Kolesar:

One of the big symptoms is going to be abdominal bloating because that’s where ovarian cancer would grow. And to have abdominal pain and abdominal bloating, the tumor has to be pretty big to cause those symptoms. And that’s really nonspecific. That could be for lots of different things.

Lauren Lavin:

And what are the current treatment options if you have ovarian cancer?

Jill Kolesar:

Usually the first thing that you’ll have is we call them a platinum doublet, which is carboplatin and Taxol. And that’s given in six cycles. And then a patient usually have surgery to remove any remaining cancer. And then after that part is done, sometimes people get maintenance therapy with this drug called bevacizumab and other people can get a targeted therapy called a PARP inhibitor.

Lauren Lavin:

So can you walk us through your recent ovarian cancer study and what makes the therapy in that study stand out compared to existing options?

Jill Kolesar:

Yeah, so we were just talking about how ovarian cancers are cold because they have, well, I guess they’re cold to immunotherapy because they have that warm environment for them to grow in, which is caused by M2 macrophages. And so we’ve developed a cell therapy that is able to go specifically to the cancer and not very many other places else. It goes a little bit to the liver, but it hones right to that cancer. And what it is able to do is to change those M2 macrophages into M1 macrophages. And when it does that, it gets rid of the nice environment and the immune system can come in and attack those cancer cells.

Lauren Lavin:

And how did you find this discovery?

Jill Kolesar:

Well, that’s a long story, and it was really a great collaboration actually. So I went to a faculty mixer, went for new faculty to find new research collaborators, and I ended up talking to some people that I wouldn’t ordinarily talk to. They were into things like 3D printing and making these things called extracellular vesicles. That’s what our therapy actually is. And I was the person who was good at getting an idea into the clinic. And so they were telling me about extracellular vesicles, and I was thinking about how we could use them. And since ovarian cancer really was such a big unmet need, we had the idea if we developed this therapy to convert the M2s to the M1s, it would make the cold tumors hot, and then they would be sensitive to the immune system.

Lauren Lavin:

How long did it take you to develop that? So once you had that idea, at what point then did you get to publish the study and use it in patients?

Jill Kolesar:

Yeah. Well, we’ve been working on it for about eight years now. So we had the idea, we got a small grant, like $50,000 to do the pilot work, and that showed us the proof of concept. So then we’re able to apply for some bigger grants. And then there’s a lot of things you have to do to be able to get your new drug all the way into a clinical trial. And so where we are right now is we’ve completed all the studies that we needed to complete, and then you basically write it up into a great big packet and you send it to the FDA and then they weigh in and say if you’re ready to go into clinical trials or not.

Lauren Lavin:

And have you done this with other drugs as well?

Jill Kolesar:

I have done it with other drugs, yes. We had a discovery, Paclitaxel, the same drug that’s used to treat ovarian cancer. We showed that Paclitaxel or Taxol was actually very synergistic with a drug called Lapatinib. And so that had not been a combination that was done before. So we did the same thing. We put this all together, went to the FDA. FDA agreed we were ready to move forward into a clinical trial. And so we completed a clinical trial in ovarian cancer of the combination, and it was successful. So we’re working on next steps with that as well.

Lauren Lavin:

Is this product an IP associated with the University of Iowa, or do you do this within a startup?

Jill Kolesar:

Yeah, so I came here a year ago from the University of Kentucky. So the IP for this drug is all at the University of Kentucky. And so when I came here, we had to have a meeting between the two IP places between Kentucky. And so now it is complicated because now [inaudible 00:11:08] discoveries in our lab here and we have this agreement about how we’re going to proceed. But both universities have been very, very collegial and willing to work together. We did also start a startup company, it’s called Vessecure. But right now Vessecure is a virtual company and basically all we’re doing is the founders put in enough money to pay for a mailbox essentially, because the big grant we got came to the University of Iowa.

Lauren Lavin:

Okay, that makes sense. So how does this work with molecular tumor boards and biomarker-based approaches help to bring discoveries from the lab setting into real patient care that’s effective for cancer?

Jill Kolesar:

Yeah, that’s a great question. Lauren, and a lot of my work earlier on in my career was looking at biomarkers and trying to predict response to therapy. But an amazing advance in my career lifetime is that we went from the lab to actually having drugs that did this. And it was just such an exciting and revolutionary thing to be part of, even in a small way. And so what happened after in the middle of my career, I decided I was going to get a master’s in epidemiology. And so I went back to school and I was on the faculty at Wisconsin at the time, and my kids were in high school so we could commiserate about our study groups. And so I went back to school. And I learned as part of the epidemiology, there’s a lot of classes that are also part of the MPH program. So I had never learned about social determinants of health.

I had never learned that it takes 10, 15 years for an academic discovery to get to out into the community. And that just made me incensed. And so I’ve had a second career with molecular tumor boards and trying to get precision medicine approaches into community medical oncology practices. So I’m from a rural area, and it really made me upset to think that my parents or my friend’s parents were not going to have access to these types of treatments. And so with a molecular tumor board, what we did is we went around and asked medical oncologists why they were not prescribing these drugs for their patients. And they basically said that, “I didn’t know anything. I didn’t learn anything about this when I was in school. I’m getting a 25-page report. I don’t know what to do with, and I don’t know how to proceed with this.”

And so what we did is we put, the tumor board was just an expert panel where people could call in and we had a meeting once a week and they call in and the panel would give them advice on what drug might be right for their patient, then it would still be the treating doctor and the patient would decide together based on this. And so we were able to implement this in Wisconsin. And then when I went to Kentucky after that, we were able to implement one there too. And between Wisconsin and Kentucky, more than 15,000 patients have been reviewed by those two molecular tumor boards. Yeah.

Lauren Lavin:

That’s incredible.

Jill Kolesar:

And about a third of them are community medical oncologists who just call in to the tumor board or they send it in and just they get written advice too.

Lauren Lavin:

Right. Well, and as I’m sure you’re very aware of, research changes quickly and I’m sure especially around cancer. And so yeah, like you said, a lot of these providers don’t necessarily have time to access all of the latest and greatest things, so having a resource like that is incredible. Do you know if any other states have something like that, or is it just those two?

Jill Kolesar:

Yeah, the VA has one. There’s one at Moffitt that I know the people quite well. There’s one in Indiana I know really well too. And the interesting thing, the one at Wisconsin, it’s a collaboration between medical oncologists and pharmacists. It was the same way at Kentucky, same way at Moffitt, same way at the VA. So it is a really great example too, where pharmacists can partner with medical oncologists to really help patients in the state.

Lauren Lavin:

Yeah, and get it to maybe underserved populations like you said, the rural. You also mentioned precision medicine. Could you define what that is just for our listeners?

Jill Kolesar:

Yeah. So at least in cancer, the way we think about precision medicine is where instead of giving everybody the same treatment, we individualize it to the patient. And a lot of the time it’s individualized based on the biomarkers.

Lauren Lavin:

And is this standard of care, or is this a pretty new approach?

Jill Kolesar:

It’s standard of care. It’s in the NCCN guidelines, and it’s been standard of care for lung cancer. It varies a little bit with the tumor type. So for lung cancer, if you have a lung cancer, a piece of your tumor will be sent to a lab and a report will come back with probably 25 different mutations on it. And depending on what mutation is there, there’s probably 10, 15 different drugs you could be potentially treated with.

Lauren Lavin:

And then they’re matched just based on your personal characteristics and your tumor type?

Jill Kolesar:

Yes, yes. Primarily the mutations in your tumor.

Lauren Lavin:

Got it. And I’m guessing that you need a lot of data in order to create those types of therapies or therapy plan.

Jill Kolesar:

Yes.

Lauren Lavin:

So how does collaboration and data sharing help to set the foundation for that as well as accelerate innovation and cancer research?

Jill Kolesar:

So that’s also another great question. So there’s a lot of publicly available databases now, and some privately held ones too, where genomic results for hundreds of thousands of patients are contained in these databases. Because the thing is, cancers are often really unique. And when you have the opportunity to put all this data into a database and to be able to search it and query it, that really amplifies the power of the advances that you can do. And it’s like with the Orion database in particular, there’s a particular company who has used that database and has really expanded the number of drugs that, and indications of drugs that are on the market. So really helping, really helping people. So it’s not just theoretical.

Lauren Lavin:

Does artificial intelligence AI play any role in the data management and the use of precision medicine?

Jill Kolesar:

Yeah, I think we’re pretty early with AI for precision medicine. So there’s a number of different databases that it would be really helpful to link together. So there’s some databases of the mutations, and then there’s some databases of the functionality of the mutations, and then there’s other databases with the drugs. And so AI linking those together would really be a tool that would help us move forward.

Lauren Lavin:

So when we’re looking at Iowa specifically and the University of Iowa, why has this place been a strong area to advance cutting edge research and women’s health research, and why were you interested in coming to Iowa specifically?

Jill Kolesar:

Yeah. Well, Iowa is just a fantastic place. Well, one of the unfortunate things though is that the incidence of cancer is actually going up in Iowa. It’s only one of two states where that’s happening. So cancer is really important here. So that’s one reason to do cancer research in Iowa. Another reason for me anyway, more personally is that the Holden Comprehensive Cancer Center is here, and I had already had some collaborators from when I was at Kentucky and from when I was at Wisconsin. And so being able to work with that group of people has just been phenomenal. There’s also a really fantastic ovarian cancer researcher here named Christy Teal, and being able to work with her has been really great as well. I guess the environment is amazing with the caliber of researchers and collaborators I’ve been able to work with. And the cancer center has really amazing shared resource facilities.

Their flow cytometry is so good, it just blows my mind. It’s really state of the art. So those are also great people to work with. And I think the other leg to the school is the University of Iowa Health System, and the DeGowin Blood Center is a cell therapy processing area. And so actually having that cell therapy processing facility on campus is really critical for our ovarian cancer trial to go forward. And I guess the fourth thing I’ll add, and I guess the fourth thing that I would add is that in the College of Pharmacy, we have University of Iowa Pharmaceuticals, which is an FDA approved manufacturing facility. And so if our trial was to advance beyond phase one, which we’re very optimistic about, then we would have access to this manufacturing facility. So I really think we have everything at Iowa from discovery to development to production for clinical trials.

Lauren Lavin:

Yeah, just a beautiful ecosystem. So is the ovarian cancer trial only happening here, or is there multiple sites throughout the US?

Jill Kolesar:

Yeah, the phase one is only going to be here.

Lauren Lavin:

And then if it went to phase two, would there be multiple sites or would it still just stay?

Jill Kolesar:

I think we probably would have to have multiple sites because there would be a lot more people in the trial if it’s a phase two, so we’d have to work with partners, so it wouldn’t take a long time to get the trial done.

Lauren Lavin:

So looking ahead, what are the next steps for your ovarian cancer work, and do you see what you’re doing in ovarian cancer extending to other types of cancer?

Jill Kolesar:

Yeah. We’re hoping to get our clinical trial going by the first of 2026, so right now we’re on track, so hopefully we stay on track. And so that would be the next thing is to start the clinical trial. And if that’s successful, we’ll move into the phase two. But with regard to other tumor types, we’ve tested it in an osteosarcoma model, so we’re ready to move forward with that. The other thing we’ve done is we’ve filled them with chemotherapy, so the little vesicles that we’re making, so they’re a nanoparticle gold that is selective for cancer, and it can be filled with just about anything. And the big advantage of that is with chemotherapy, it goes everywhere in the body and it causes a lot of toxicity. It’s not precision medicine at all, but this would be a way of making chemotherapy a precision medicine, because we would put it in these vesicles and it would go right to the cancer and only kill the cancer cells and not have toxicity, and that’s exactly how it works in mice.

Lauren Lavin:

This reminds me of we’re now getting to the point in cancer care where we’re trying to alleviate some of those side effects. And I think that’s a really cool place to be headed.

Jill Kolesar:

Yeah, I’m excited about it.

Lauren Lavin:

Yeah. Well, thank you so much for chatting with me today. I really appreciate you taking time, and I learned a lot in this discussion.

Jill Kolesar:

Well, thanks again for having me. It was really fun to talk to you.

Lauren Lavin:

That’s it for our episode this week. A big thank you to Dr. Kolesar for joining us and sharing her insights on ovarian cancer research, precision medicine, and the power of collaboration in advancing cancer care. In today’s episode, we learned how innovative cell-based therapies may help transform cold tumors into ones that can respond to the immune system, why ovarian cancer presents unique treatment challenges, and how molecular tumor boards can bridge the gap between cutting edge genomic science and real world clinical practice. We also discussed the importance of ensuring that advances in precision medicine reach rural and community settings and not just major academic centers.

This episode was hosted and written by Lauren Lavin and edited and produced by Lauren Lavin. You can learn more about the University of Iowa College of Public Health on Facebook. Our podcast is available on Spotify, Apple Podcasts and SoundCloud. If you enjoyed this episode and would like to help support our podcast, please share with your colleagues, friends, or anyone interested in public health. Have a suggestion for our team? You can reach us at cph-gradambassador@uiowa.edu. This episode was brought to you by the University of Iowa College of Public Health. Until next week. Stay healthy, stay curious and take care.