Expanding Precision Oncology with Thai Ho, M.D., Ph.D.

MUSC Hollings Cancer Center is establishing a new precision oncology program and a precision oncology tumor board, which will improve cancer care across South Carolina. Thai Ho, M.D., Ph.D., leads this effort and, in this episode, shares more on the board as well as insight into precision oncology offerings at Hollings and his expertise in treating and studying kidney cancer.

“We're further extending to not only the clinical data that we see when we look at patients; we're also looking at the molecular tests. So, it's integration of both the clinical side with the molecular test, to better inform decision making for patients.”
—Thai Ho, M.D., Ph.D.

Topics Covered in This Show

• MUSC Hollings Cancer Center is at the forefront of tailoring cancer treatments based on patients' DNA or cancer tumor DNA to offer targeted treatments that could be more effective than traditional chemotherapy while reducing side effects.
• Ho leads the new precision oncology program and a precision oncology tumor board at MUSC Hollings Cancer Center in an effort to integrate clinical and molecular data for informed decision-making in cancer treatment.
• MUSC offers both germline and somatic genetic testing. Germline testing looks at inherited DNA alterations, while somatic testing analyzes DNA alterations present only in the tumor. Understanding these differences helps in personalized treatment and preventive measures for inherited syndromes.
• Through the new precision oncology tumor board, there will now be a multidisciplinary group of specialists, including bioinformaticians, molecular biologists and ethicists, to integrate clinical and molecular data for informed decision-making in cancer treatment and to prevent cancer rather than waiting until it develops.
• Ho is sensitive to the financial burdens cancer patients face as well as ethical concerns that arise around genetic information usage. These are all important considerations he will be taking into account as the center creates new opportunities for genetic screening, testing and precision medicine.
• Along with his clinical duties, Ho is a scientist focused on studying kidney cancer, particularly addressing immune therapy resistance and studying the SETD2 gene mutation. This mutation can be associated with more aggressive variants of kidney cancers. However, there are no known drugs that target this gene. He hopes to identify what targets could be used from drugs that are already approved by the government for other tumor types and apply them to treat this form of kidney cancer.
• MUSC has the latest innovations in kidney cancer treatments, and Ho says it's very important for patients to come to a center that can offer all these different options so that they have the best chance of cure because once the tumor spreads to outside the kidney, it cannot be cured.

Read the Transcript

[00:00:00] Erin Spain, MS: Welcome to Advance with MUSC Health. I'm your host, Erin Spain. This show's mission is to help you find ways to preserve and optimize your health and get the care you need to live well. There's an exciting new program under development at MUSC Hollings Cancer Center, dedicated to precision oncology, where doctors will be tailoring cancer treatments based on a patient's DNA or the DNA of their cancer tumor. Leading this effort is Dr. Thai Ho, a physician-scientist who treats genitourinary cancers and aims to translate bench discoveries into patient care and his lab. Dr. Ho joins us today with a preview of how the precision oncology program and a precision oncology tumor board will improve cancer care across South Carolina, he will also share expertise in kidney cancer care and research. Welcome to the show.

[00:00:59] Thai Ho, M.D., Ph.D.:: Thank you for having me.

[00:01:00] Erin Spain, MS: You are new here, and you will be heading up this new effort, the precision oncology program, and a precision oncology tumor board. Tell me a little bit about your background and your work as a physician-scientist.

[00:01:13 ] Thai Ho, M.D., Ph.D.: I was originally born in Japan, and then I lived in Belfast, Ireland, New York City, Texas. I was on faculty at Mayo Clinic Arizona for the past 12 years before coming to MUSC. As a physician-scientist, my goal is to identify things that are unique to patients in the clinical side, take it into the laboratory, study it further, and then bring it back to the patient. So the goal is I can seamlessly navigate the sides of both clinical, where you're seeing patients, as well as preclinical, where you're trying to use different actionable targets or gene alterations for the purposes of designing new drugs.

[00:01:50] Erin Spain, MS: Tell me about precision oncology and how that's taking place here at MUSC Hollings Cancer Center.

[00:01:56] Thai Ho, M.D., Ph.D.: This is something that physicians have already been using at MUSC. One of the things that we like to do here is try to identify how a tumor is driven by certain genes and certain drugs target those certain genes. The advantage of doing that is sometimes patients don't necessarily need to undergo chemotherapy. Instead, they take pills. And that has the same effect, if not better effect, than chemotherapy and spares patients of side effects while having increases in shrinkage of tumors. So the goal of these precision medicine analyses is try to identify which tumors might respond better to pills better than chemotherapy, and that could spare patients of some of the side effects associated with traditional chemotherapy.

[00:02:39] Erin Spain, MS: That really illustrates how powerful genetic screening can be. Tell me a little bit more about some of the genetic screening that is offered to patients at MUSC Hollings cancer center.

[00:02:50] Thai Ho, M.D., Ph.D.: Any patient that comes through MUSC has an opportunity to undergo genetic screening looking at what we call germline testing. So this is looking at DNA and genes that could be inherited from mom and dad. This can be accessed through talking to your physician or getting a referral to medical genetics. The other opportunity for genetic testing is actually having your doctor order testing on the tumor that's removed from your body. This is what we call somatic testing. The key difference between somatic testing and germline testing is that with germline testing, this is something that's inherited from Mom and Dad, and that can be passed on to children, brothers, and sisters. Whereas somatic testing means that DNA alteration only occurs in that tumor and that's not inherited. So that really affects the patient, whereas germline testing can affect the patient and their loved ones. There are certain syndromes where if a patient inherits an alteration from Mom or Dad, the risk of their children also developing the same syndrome is 1 in 2, so 50%. For patients who have genes where they're inherited from Mom and Dad, we can actually attempt to prevent cancer or look for cancer before it occurs. And this is where the impact of these genomic tumor boards and evaluating the DNA of patients comes into play because you can actually attempt to use it to prevent cancer rather than waiting till it develops.

[00:04:10] Erin Spain, MS: You mentioned the precision oncology tumor board. Now you are working on bringing that together here at MUSC Hollings Cancer Center. What is that going to look like, and who would be on the board?

[00:04:23] Thai Ho, M.D., Ph.D.: So this is a natural extension of existing tumor boards that we already have for various tumor types. Typically, patients who come to MUSC are presented at a tumor board, where this comprises experts from medical oncology, hematology, pathology, surgery, radiation oncology, radiology and pathology. But adding an additional layer of the genomics tumor board means we now have specialists that are added that include bioinformaticians, molecular biologists, medical geneticists, ethics, physicians with expertise in pharmacogenomics and pharmacology. So what we're doing is we're further extending to not only the clinical data that we see when we look at patients, we're also looking at the molecular tests. So it's integration of both the clinical side with the molecular test, to better inform decision-making for patients.

[00:05:15] Erin Spain, MS: Tell me about the power of that multidisciplinary board coming together.

[00:05:20] Thai Ho, M.D., Ph.D.: Because of the nature of cancer, it takes sort of a whole team to take care of a patient, much like when you play football, you have people who are specialized in certain positions. Similarly with your medical oncologist, your surgeons, they have certain techniques they're able to utilize and they can utilize it with the assistance of other physicians. So by having a whole team of physicians treating a patient, you can sort of pull from the expertise from multiple disciplines to get the best care for the patient.

[00:05:48] Erin Spain, MS: Tell me about some of the challenges that you anticipate facing as we talk more about genetic screening of patients.

[00:05:55] Thai Ho, M.D., Ph.D.: I think there's always a concern from patients in terms of co-pay costs, how much is it going to cost them. This is something that we have to be very sensitive to because for a cancer patient, they have Medicare Part B as Medicare Part D. And there's a certain deductible that you have to make. So, let's say you have a $5,000 deductible on anything that's injected, another $5,000 deductible on pills. On top of that, you're adding $300, $400 worth of testing, plus transportation. You can quickly see how these little small numbers add up to a significant financial burden for all our patients. And these are patients who you know, who may not have financial resources to cover all this. So I think one of the things that we have to do is minimize the financial toxicity to our patients. The companies that we work with, the platforms that we work with, have made it a priority to offer genetic testing to patients, irrespective of their ability to pay. Two, I think, in terms of patient education, is understanding how this information will be used. I think there's always a concern that there may be misuse of this genetic information where insurance companies would potentially change benefits or deny patients coverage based on the results of these genetic tests. And this is something that the medical profession as a whole has to do better in terms of communicating to the patients, uh, what the implications of these tests are. Then third, I think also getting patients to understand the differences between something that's inherited versus something that's only in the tumor, because I think that's a big difference in how we manage some of these tumors.

[00:07:33] Erin Spain, MS: I want to talk about your lab and your role as a physician-scientist. Tell me about the work that you're doing and what you're studying.

[00:07:41] Thai Ho, M.D., Ph.D.: So a lot of things in my laboratory are focused on kidney cancer, so one of the things that I'm working on in kidney cancer is trying to overcome what happens when patients fail immunotherapy, so we know that we can use the immune system to fight the cancer, but at some point the tumor becomes resistant to it. And one of the things that we're doing now is we're trying to overcome that prior resistance to the immune therapy. So is there some way that we can restore the immune system to fight the kidney cancer? Or can we kind of help the immune system when it's not working as well by adding another drug? That would target some of these genes, such as SETD2 in kidney cancer to give it an extra boost to get the patient's immune system back online.

[00:08:24] Erin Spain, MS: You mentioned the gene SETD2 that occurs in kidney cancer. You've done quite a bit of research on this gene mutation. Tell me about this work.

[00:08:33] Thai Ho, M.D., Ph.D.: One of the unique things about kidney cancer is that it doesn't have the traditional mutations that we see in other cancers like TP53, KRAS. These mutations that we see in kidney cancer alter how the DNA is read. It also controls how the structure of DNA is controlled inside the nucleus of the brain of the cell. As part of that, the gene SETD2, if it's altered at a young age, this can lead to developmental delay. It can change how patients think when they're younger, and then in adult patients, when there's mutations, particularly in tumors, this can be associated with more aggressive variants of cancers. However, despite having a gene that we know is involved in cancer, we don't have any known drugs that target this gene.

[00:09:21] Erin Spain, MS: So, what are you doing in your lab to address this?

[00:09:24] Thai Ho, M.D., Ph.D.: So we're studying tumors from patients affected by these mutations. We've also identified ways of making mouse models and engineering these mutations. And what we're trying to do is identify what targets that we could use from drugs that are already approved by the government for other tumor types and apply it to which drugs we could also reuse for the purposes of treating cancer. By doing this, what we're trying to do is circumvent the toxicity profile associated with different drugs. So we have different phases of trials. We have phase 1, phase 2, phase 3. Phase 1 trials are first in man, first in woman drugs, and often these drugs are being tested just for toxicity and a lot of our drugs that we test often fail in this area because it ends up being very toxic for our patients. So by using drugs that are already approved by the government, we at least know what the toxicity profile is going into it, and we could reuse that drug for other diseases.

[00:10:21] Erin Spain, MS: How many people who have kidney cancer have this specific type of mutation in the SETD2 gene?

[00:10:28] Thai Ho, M.D., Ph.D.: It's about 10 to 15 percent of patients affected by kidney cancer. If you look at the number of kidney cancers diagnosed in the United States, it's about, 75, Americans, and that counts for about 4 percent of all new cancers.

[00:10:41] Erin Spain, MS: Kidney cancer, though, is one of the top 10 cancers that Americans are diagnosed with. Tell me about kidney cancer and how it affects people.

[00:10:51] Thai Ho, M.D., Ph.D.: So your kidneys are these bean-shaped organs, it's about the size of a fist, and what they're responsible for is for filtering the waste from the body. So that when we get rid of the waste in our urine, it essentially allows us to excrete that waste. So all of our waste that we generate from our cells is either excreted in our feces or our urine. Kidney cancer arises from that organ that filters the waste, and if not controlled, it can spread to other parts of the body, including the lungs, the lymph nodes, the brain, and the bone.

[00:11:20] Erin Spain, MS: There does seem to be a rise in the diagnosis of kidney cancer. Tell me about that.

[00:11:27] Thai Ho, M.D., Ph.D.: So, one of the challenges with kidney cancer is we don't have a screening test like we do in breast, colon, cervical cancer, breast cancer. In many cases, there aren't any symptoms, and they're randomly found while someone is being evaluated by a doctor for other reasons. Symptoms may include abdominal pain, unexplained weight loss, blood in the urine, fatigue, or fever. Some of the risk factors are associated with older age, obesity, smoking, high blood pressure, any prior history of kidney failure, inherited syndrome, so these may be situations where the patient has inherited a gene from either mom or dad that puts them at risk of kidney cancer. So some of these things are, things that are on the rise, like obesity, and as our patients age, this also increases as well. We also know there's been a link. So, this is a very important link between service and kidney cancer. So, this is also one of the service-connected conditions that we have for patients who have served in our military.

[00:12:24] Erin Spain, MS: So today, if you're diagnosed with kidney cancer and it has not spread, what is the treatment? What are the different options?

[00:12:31] Thai Ho, M.D., Ph.D.: So, once diagnosed with kidney cancer, it's very important to come to a place that's comfortable with analyzing the tumor comprehensively for the purposes of the best outcome. Because when a tumor is localized, that's generally your best chance of cure. So MUSC has the latest innovations in kidney cancer treatments, where they can use a patient's own immune system to fight the cancer. They can do surgeries that are minimally invasive, and maximize the tumor removal without compromising the removal of the normal kidney. With these localized cancers, we can use radiation, we can heat them up, we can freeze them, and this may be an option for patients who can't undergo surgery, so it's very important for patients to come to a center that can offer all these different options so that they have the best chance of cure because once the tumor spreads, to outside the kidney, this is what now what we consider to be stage four or the highest stage of cancer where we're just trying to buy the patient's extra time but we're not, unfortunately, able to cure a lot of these cases once it becomes stage four.

[00:13:38] Erin Spain, MS: The last question is the question we ask everyone on the show, and that's, what do you do to optimize your health and live well?

[00:13:45] Thai Ho, M.D., Ph.D.: So I think exercise is important. I like to exercise every day, I walk to work, take the stairs when I can, knowing that, for instance, at least kidney cancer, it's associated with obesity, high blood pressure; these things are very hard to treat with medication alone. These sometimes often require some sort of lifestyle modification. And I think the healthier you are going into treatment, if you are unfortunately affected by cancer, typically the better you'll be able to deal with the side effects. Whereas, if you have more problems with being sedentary, not able to exercise. Sometimes it can be very difficult because the side effects really wear you down. Whereas if you have a generally healthy lifestyle, it allows you to deal with the side effects a little bit better.

[00:14:29] Erin Spain, MS: Thank you for all that you're doing to improve cancer care across South Carolina. We're happy you're here.

[00:14:35] Thai Ho, M.D., Ph.D.: Thank you for having me.

[00:14:36] Erin Spain, MS: For more information on this podcast, check out advance.musehealth.org.