Karie Dozer [00:00:05] I'm Karie Dozer, and this is TGen Talks. As the second most common cause of death in the United States. Cancer research is a huge focus at TGen, where researchers study many types of cancer, including lung and colon cancer, pancreas and blood cancer and cancers affecting children. On this edition of the show, we talk with a researcher who specializes in cancers of the brain, and who study findings may help doctors more precisely choose the best available treatment for each individual brain cancer patient.
And here with me for this episode of TGen Talks is Dr. Floris Barthel, who's only been at TGen for it seems like a matter of minutes. You're kind of a new guy around here. Thanks for joining me. Can you tell me what your title is here at TGen?
Dr. Floris Barthel [00:00:55] Absolutely. I'm just really happy to be here. Thanks for the invitation. So I am an assistant professor here at TGen in the Cancer and Cell Biology Division. But I also have an appointment with City of Hope as an assistant professor at the Department of Computational Quantitative Medicine. And I also have appointments at Arizona State University and the University of Arizona as an adjunct assistant professor.
Karie Dozer [00:01:21] Sounds really busy, yet you managing to do some pretty important research.
Dr. Floris Barthel [00:01:25] I hope so. Yeah, I hope so.
Karie Dozer [00:01:27] What is your area? What was your area of study and expertise and what made you choose the field?
Dr. Floris Barthel [00:01:34] Yeah. So I work in cancer genomics specifically looking at brain tumor genomics. Genomics means essentially now we're looking at the DNA of tumors and specifically, we're looking at how tumor DNA is different from the DNA that we inherit from our parents. And how did I get into that? You know, I think … I went to medical school and I became fascinated by the brain and how the brain works. And I got really interested in oncology and I saw a lot of patients suffering from brain tumors, and that really empowered me to move into this field.
Karie Dozer [00:02:12] It seems like a steep hill to climb. People hear that the term brain cancer, a brain tumor, and they think there's nothing left to fight that humans always lose that battle. Was that part of it? What made you go into a field that seemed so daunting?
Dr. Floris Barthel [00:02:28] Yeah, you could say that's part of it. It's absolutely the case that the specific there are. Fortunately, there are some types of brain tumors that are very curable and that have a very good prognosis. But, unfortunately, many of them don't, and many of them actually have a very severe prognosis and severely impact the patient and their family and loved ones. And that was definitely a motivation for me to move into that field,
Karie Dozer [00:02:58] This might be to general a question, but how many different kinds of brain cancer are there?
Dr. Floris Barthel [00:03:04] You know, I don't actually know the number. There are a lot. There are hundreds but many of them are really small and rare subtypes, and usually it tends to be the case that the more rare the brain cancer, the better prognosis. All right. So the better the patient does. It's unfortunately the more common ones that tend to be more aggressive and tend to have the worse prognosis.
Karie Dozer [00:03:32] Fundamentally speaking is the study and treatment of brain cancers very different from the study and treatment of other cancers?
Dr. Floris Barthel [00:03:40] Yes and no. No. Because many cancers, we still use the same types of treatment regimens to treat these tumors. Chemotherapy and radiotherapy, probably most people have heard of those. Those two modalities treatment are essentially used for all types of cancers, regardless of whether it's the brain, the liver, the lungs or the kidneys or any other organ for that matter. What makes brain cancer different is, I think, especially when it comes to chemotherapy or essentially drugs, drugs have a much harder time reaching the brain because of a barrier known as a blood-brain barrier that makes driving the brain especially difficult.
Karie Dozer [00:04:31] That brings me to my question about your area of research and your study, and essentially, I assume why you're here at TGen. More than half of cancer patients at some point are treated with radiation therapy. Is that the area that you chose to study? And if so, why? Is there a big question you were you were trying to answer?
Dr. Floris Barthel [00:04:52] Yeah. So in general, my lab and also my postdoc, we looked at brain tumor genomics, which is really just looking at the DNA of brain tumors and how it differs from normal DNA. So radiotherapy is something that we started looking at because one of the things that we were so interested in is understanding why it is that with brain tumors, no matter what we do, no matter how we treat them, the tumor always comes back. Many patients, if they're … if they're fit enough to have another surgery to go through another round of treatment, they will want to do that. And that will be what we do. We wanted to see if we could we could now look at the tumor when it comes back and then take the second tumor and compare it to the first tumor and to kind of see what has now changed in the DNA of the tumor over time. People are typically before that are really only looked at the first tumor. Now what is it? What is different in the DNA of the first tumor compared to the normal DNA? Now we're looking at what's different in the second tumor compared to the first tumor compared to the normal DNA? And so we specifically started wondering, well, what happens with treatment, right? And how does treatment actually affect the DNA of these tumors over time?
Karie Dozer [00:06:13] So if drug therapy is less effective with brain tumors, you're obviously looking at the majority of cancer patients with brain tumors who have been treated with radiotherapy. And you're trying to answer the question how is their tumor different? The second time or the third time those recurrences, what did you find?
Dr. Floris Barthel [00:06:31] Yeah. So one of the things we looked at right is when we treat a tumor with radiotherapy and radiotherapy. The way it works is that radiotherapy causes these little breaks in the DNA, right? And that's what we wanted to do. We wanted to break the DNA because cells that have broken DNA and DNA is really important because it's the blueprint essentially for the cell, and it tells us how to do what it does, what it's good at. And so if it's broken, it'll typically cause a cell to die. And so that's what we want to happen to tumor cells, right? We want those. We want those DNA breaks. We want to sell to die and the tumor cells to go away. That's what we're what we're expecting to kind of see. The alternative scenario right is where the DNA doesn't and where the DNA maybe breaks, but then before the cell dying, it actually gets repaired. And so the break gets stitched back together and the broken ends of DNA get stitched back together. But usually when that happened, it's not a perfect fix, right? And so what you'll see is that letters in the DNA will have whatever have disappeared. Sometimes maybe a letter was added. Maybe sometimes you can see letters was changed. And so you kind of have this imperfect repair process going on in response to radiation. And so we kind of knew in theory that this was always happening. But what we were seeing, what we wanted to see is now having all these, you know, I think we had about 250 patients that had been, you know, treated in one way or the other. Can we actually see differences in patients that were treated with radiotherapy and that were not treated with radiotherapy? And so indeed, we saw that. So we still saw that patients that were treated in radiotherapy showed all these small deletions in their DNA. Moreover, some patients showed more deletions than other patients, which also gave us an idea that maybe the amount of deletions that we can see can actually be some sort of way to quantify how much DNA repair there is ongoing and more DNA repair, essentially meaning that the tumor is more resistant to radiotherapy because it's more able to deal with those DNA breaks, which is
Karie Dozer [00:08:52] exactly the wrong thing to happen. In other words, for treating patients with radiotherapy to kill the tumor, and after a certain point, you were finding that the more times you went after that tumor, the more resistant it became to future radiotherapy.
Dr. Floris Barthel [00:09:06] Yeah, yeah. I mean, I think I think it's I don't want to refute the evidence that radiotherapy isn't a good thing, right? I think it's it's very important that we treat these patients with radiotherapy. It's very effective. But what this is and whether or not the patient, the tumor could become stronger, it's also disputable. I mean, we see in the evidence that that patients who get treated with radiotherapy generally benefit from the treatment. They live, they live, they live longer, they do better. What it can help do is now maybe tease out patients that have, you know, we've treated with radiotherapy once and we kind of saw after that first treatment, well, they're pretty resistant to radiotherapy. Well, maybe we could say, well, if we're going to treat them again, because typically after they have that second surgery that you know, they'll be subject to another round of treatment after that. So it's, you know, you have your surgery. Well, now what do we do next to which we give additional chemotherapy? Do we give initial radiotherapy a combination thereof? Or are there other drugs we can try? Are there other trials we can enroll them in? But this could be helpful to say, Well, maybe. You know, this particular patient, the first time we gave them radiotherapy, they were pretty resistant to it, maybe we should not give them radiotherapy again.
Karie Dozer [00:10:30] Your study didn't seek to determine whether or not radiotherapy is still a good option, it's often still the best first option, but it might not be the best second or third option for a particular patient.
Dr. Floris Barthel [00:10:45] Yeah, I think well, yeah, but yes, but more studies are really needed to really precisely be able to quantify that. What we're just seeing is how is radiotherapy changing the DNA and all of these tumors. And that's previously it's really been only known to the sense that we kind of from a textbook perspective, are we say, Oh, well, radiotherapy causes DNA breaks and causes deletions, but it's never really been measured. And so we're now we're actually able to quantify titrate the amount of deletions and the amount of mutations that this is leading to in patients. And we're now able to separate patients, maybe on those that respond better and respond worse.
Karie Dozer [00:11:33] Well, part of the TGen mission is about more personal treatments, more precise treatments. Is there a day in the future that you hope that everyone who's diagnosed with a brain tumor of any kind has that kind of specific treatment that we are treating your brain tumor? Not the type of brain tumor that you may present with?
Dr. Floris Barthel [00:11:54] Well, absolutely. I think that's where all of us are kind of moving towards. And this is just one small, one small step along the road because there's so much we need. We still don't know and so much we need to do to get there. And so every little step helps, right?
Karie Dozer [00:12:14] It seems like the more you know, in other words, the more studies come up with a definite concrete conclusion, the more you realize more research needs to be done. Is there enough time in the day?
Dr. Floris Barthel [00:12:26] Yeah, that's the million dollar question, I think. It seems that every study we do reaches more questions, but I think every study also moves us, move the field forward just a little bit and just a little bit to stay optimistic that that that that that we're really making progress here and that, you know, we can change practice and that we can find a cure to brain cancer.
Karie Dozer [00:12:54] What is next for you at TGen if when this particular study, this particular question seems answered, what is next? What would you like to do?
Dr. Floris Barthel [00:13:05] So actually, right now, my lab is really focused on the ends of chromosomes. So our DNA is packed into these units called chromosomes. And so at the end of the at the end of these, these units of DNA, there is this segment called the telomere. And so we know that these segments shortens with which with each cell division and in cancer, they can be particularly short, particularly long, or they can be all sorts of different shapes. And it's really important for cancer cells to be able to maintain this DNA because we know that when they are when these DNA segments are too short, they become dysfunctional, meaning they can be quickly rearranged to take all sorts of other different conformations. And that could be beneficial to the to the tumor in the sense that it could make the tumor more aggressive or acquire mechanisms due to become more resistant to therapy, to become, you know, more and more and more aggressive. And so we're studying that from a genetic point of view, looking at the specific DNA sequences, but also from an epigenetic point of view, looking at the confirmation that DNA takes in sort of 3D space and how it interacts with the gene DNA just being essentially the blueprint of cells. But actually another important molecule being RNA, which is really pieces of smaller pieces of DNA that contain the specific instructions to make proteins, which actually do all the actions. And so how conformational changes in of telomeres can actually affect how RNA molecules are transcribed from DNA. So that's another field of study.
Karie Dozer [00:15:07] So anything that I missed, anything that you wish I had asked about your research or your lab that I did not.
Dr. Floris Barthel [00:15:13] Yeah, so well, that's one area specifically looking at telomeres, both genetics, DNA, epigenetics, you know, other than DNA. Another area that we're really interested in is continuing this work on. Specifically glioma, but now looking at liquid biopsies where we can take, for example, samples of blood and in a similar fashion to how we're looking at radiotherapy, how it's changing the tumor DNA, can we now follow the tumor over time by simply looking at looking at the blood patient's blood? So patients have had a tumor? You know, one of the biggest question is especially with brain tumor, because like I mentioned, unfortunately, it always comes back, right? But how do we identify when it comes back? Typically, we'd look on an MRI scan, right?
Karie Dozer [00:16:07] But you don't want to wait until a patient has symptoms of a brain tumor. Yeah.
Dr. Floris Barthel [00:16:11] And typically when sometimes with a MRI scan, you might be too late. Right. So can we catch it earlier by looking just at a sample of blood, which is so much easier to obtain? So that's another area of research that that that that where
Karie Dozer [00:16:28] you already have five jobs, are you going to have to look for that one?
Dr. Floris Barthel [00:16:32] Well, I'm, you know, I have a great team of a great team that that, you know, I've only been here for a couple of months now, but I already have a couple of great people working, working with me and working on answering these questions. And I'm definitely looking to expand. You know, maybe I can actually use this as a shout out. If there's anybody in science who loves to study brain tumors, is interested in DNA, is interested in genomics. You know, look me up and there is, you know, we're looking to expand our team and, you know, work on the work on these questions.
Karie Dozer [00:17:04] There you have it. It's the first casting call we've ever had on TGen Talks Dr. Florence Martel. Thanks for joining me. Absolutely. For more on TGen research into brain cancer and other types of cancer, go to TGen Talks. TGen, an affiliate of City of Hope, is an Arizona based nonprofit medical research institute dedicated to conducting groundbreaking research with life changing results. You can find more of these podcasts at tgen dot org slash tgen talks or on Apple Podcasts. For TGen Talks, I'm Keri Dozer.