Making the Rounds

Treatment efficacy research of neuroblastoma tumors in children, 2022 AMA Research Challenge

Nov 22, 2022

In this episode of Making the Rounds, AMA Research Challenge finalist, Kanita Chaudry shares her research on the efficacy of a treatment for neuroblastoma cancer tumors in children. Kanita Chaudhry is an MD-PhD student at the University at Buffalo's Jacobs School of Medicine and Biomedical Sciences.

Speakers

  • Kanita Chaundry, MD, PhD, student, University at Buffalo's Jacobs School of Medicine and Biomedical Sciences
  • Brendan Murphy, senior news writer, American Medical Association

Host

  • Marielisa Cabrera-Sánchez, 2021 AMA Research Challenge winner

Listen on the go to the full episode on Apple Podcasts, Spotify or anywhere podcasts are available.

Cabrera-Sánchez: Welcome to Making the Rounds, a podcast by the American Medical Association. I’m Marielisa, last year’s winner of the AMA Research Challenge, which is the largest national, multi-specialty research event for medical students, residents and international medical graduates.

Today’s interview features one of this year’s five finalists for the 2022 AMA Research Challenge, interviewed by AMA Senior News Writer Brendan Murphy.

Murphy: Hello and welcome to Making the Rounds by the American Medical Association. I'm Brendan Murphy, senior news writer here at the AMA. Today we are interviewing Kanita Chaudhry, a finalist in the 2022 AMA Research Challenge. Kanita is an MD-PhD student, doing the research portion of her studies at University at Buffalo's Jacobs School of Medicine and Biomedical Sciences. Hello, Kanita. How are you today?

Chaudhry: I'm doing well. Thank you.

Murphy: Kanita is one of five finalists in the AMA Research Challenge. Her poster is entitled, “The Aryl Hydrocarbon Receptor as a Novel Therapeutic Target in Neuroblastoma.” Kanita, we're looking forward to hearing so much about your research. So, let's get started with a few questions. Could you tell us a little bit about this topic? Why it appealed to you? And how you got involved in the Research Challenge?

Chaudhry: Yes. I became very interested in cancer biology when I was an undergraduate student at the University of Vermont. And later, I watched my mom get diagnosed and treated for breast cancer. So, I was drawn to Roswell Park Comprehensive Cancer Center for my MD-PhD studies.

And currently, I'm working in the lab of Dr. Anna Bianchi-Smiraglia, where I'm studying neuroblastoma, which is the most common extracranial tumor in children. And there is a desperate need for novel therapies for neuroblastoma because despite the fact that these patients receive intensive multimodality treatments that are really toxic, approximately half of these high-risk patients die due to relapses. And these relapses occur from resistance to existing therapies such as retinoic acid.

And MYCN is one of the major drivers of neuroblastoma disease progression. Patients that have MYCN amplification have poor prognosis and poor response to retinoic acid treatments. And that makes MYCN a very attractive drug target. But there's no drugs that can currently target MYCN. And so much of the research that's focused now is on understanding, how can we indirectly target MYCN?

So, in my current project, our work identifies the aryl hydrocarbon receptor or AHR, which is a transcription factor as a novel therapeutic target in neuroblastoma. We found that AHR is a novel tumor promoter that regulates MYCN and alters response to retinoic acid treatments.

And a very exciting part of our work is that we are using Clofazimine, which is currently FDA-approved for the treatment of drug-resistant tuberculosis and lepromatous leprosy, as a novel AHR antagonist. And Clofazimine is given orally in patients. It's very safe with minimal side effects. And it's very cost-effective. It only costs $20 a month.

And we found that Clofazimine treatment decreased neuroblastoma growth. It reduced MYCN levels. And it improved response to retinoic acid treatment. So Clofazimine could be a potential and promising new therapy that could be rapidly repurposed for neuroblastoma patients in the clinic.

In terms of the AMA Research Challenge, I kind of became involved by accident. I'm usually on the lookout for opportunities to enrich my academic experience. And one day I received some emails from the AMA advertising this research challenge and without thinking too much about it, I decided to submit an abstract. And so, I'm very grateful to have been selected as a finalist. And I'm very happy that I can share my work and educate people about this very important topic.

Murphy: Well, we're glad to have you. And this is, of course, a very important topic. It is certainly an ambitious topic for a medical student to take on. What were some of the challenges you encountered in doing this research?

Chaudhry: So day-to-day in the lab, it's normal to experience technical challenges, for example, the reagent that you use doesn't work. Or when you start a new assay, you have to spend time optimizing it for your particular experiment. And I've experienced many of those technical challenges.

But apart from that, some of the challenges that were unexpected before I came to this project were just related to studying a pediatric cancer. Because there's less resources and less funding opportunities available in this area, compared to adult cancers like breast, or lung, or prostate cancer. And we are the first lab at Roswell Park to study neuroblastoma. And so many things have to be built from the ground up.

We recently acquired human neuroblastoma patient samples from the Children's Oncology Group. But it took us more than six months to even get those samples before we can start doing experiments. We also don't have all of the mouse models. There is a genetic model of making amplified neuroblastoma but we don't have the money or resources to establish the colony yet. But fortunately, we have been very grateful to collaborate with other physicians and scientists who are helping us.

And one of our collaborators on this project is Dr. Michelle Haber, who is the director of the Children's Cancer Institute in Sydney, Australia. And she's a world-renowned expert in this area. She's helping us with some of the experiments in human neuroblastoma patient samples.

Murphy: Well, that is all pretty fascinating work you're doing. And as I said, it's really impressive that you're doing it as a trainee. Looking at your experience and how it might be valuable to other trainees, what advice would you offer to medical students or residents even, who are conducting research on a highly technical topic like you did?

Chaudhry: I think my biggest piece of advice in general for anyone who wants to do research is to choose a supportive mentor. And I've been very grateful to have a very supportive mentor Dr. Anna Bianca-Smiraglia, who without her guidance and support, I don't think we could be—I could be successful.

For highly technical topics, I think it's very important to get dedicated one-on-one mentoring from a more experienced person, who is willing to teach you techniques at the bench. And I had that opportunity to get close mentoring. And it really helped me become efficient in the lab, so that I could focus on answering questions rather than struggling to learn the techniques.

I also think it's very important not to be afraid to ask for help and to be resourceful. A few months ago, I was working on an experiment no one in my lab had done before. And I ended up finding a paper, where it was successfully done at another institute. So, I emailed that professor, and he very generously shared his protocol with me. So, because of his help, we were able to make good progress on the project.

Murphy: So certainly, you can build off the work and success of others. And it does seem like there are willing mentors and willing faculty members elsewhere, other researchers who are just working to advance this type of work. In that vein, what do you see for the next steps in this particular research project?

Chaudhry: So, we definitely have much more to do. And my project—and my findings open up so much more questions. So right now, we are working on testing the efficacy of Clofazimine alone and in combination with retinoic acid in a mouse model, to see if AHR inhibition with Clofazimine can enhance retinoic acid effectiveness in reducing tumor growth in people. We just started this experiment last week, so we should get an answer in the next week or two.

We're also doing a lot of experiments right now, to understand the mechanisms by which AHR regulates neuroblastoma differentiation and how it regulates MYCN. Very interestingly, we found that AHR acts as an epigenetic regulator and that it acts as a chromatin remodeler. And so that's going to be very important to understanding how we can develop even better therapies for neuroblastoma. Ultimately, if our mouse experiments work with Clofazimine, we would like to start clinical trials in patients with Clofazimine.

Murphy: It sounds like you've got a good idea where this is going to head in terms of the work. In terms of your career, how will this research impact where you see yourself going? Will it affect your specialty choice?

Chaudhry: Yeah. So, I've always been dedicated and committed, or interested in becoming a physician-scientist but not really sure what field I wanted to focus on. This research experience has motivated me to focus on pediatric oncology, which is a very understudied area in the research area. I just think that there's a major need for new therapies. And helping a pediatric cancer patient, gives them life throughout their whole life. And I think that is really special.

So for my future career, I want to see and care for pediatric cancer patients in the hospital. But I also want to run a lab, where I can pursue the kinds of projects that I am right now. I want to understand the mechanisms that drive cancer progression and how we can use that to develop new therapies. And ultimately, I'd like to work at a cancer center that allows me to bring my research findings to the clinic through clinical trials.

Murphy: That is really some vital work. And I know that both patients and the profession will appreciate your contributions to that realm of medicine. What else should our listeners know about your journey in medicine?

Chaudhry: I'd say that while I've always had a focus to become a physician-scientist, I've definitely experienced bumps along the way. I was admitted to medical school very late. And I doubted my ability to get accepted into MD-PhD programs. And I feel very lucky that I've had this opportunity. And when I got into the lab, I experienced difficulties. My project didn't go anywhere for two years. I had a lot of rejected grant applications. I had an advisor move away, so I had to start again from scratch.

But I believe that if you're really dedicated, and you're really passionate about what you do, and you keep working hard and trying, that you'll eventually be able to reach your goals. And I think it's important to find the right environment and surround yourself with people who have your best interest and support you. I'm very grateful for my mentor, Dr. Anna Bianchi-Smiraglia for her support on this project. And I'm also very grateful for the support that I've received from the MD-PhD program at the Jacobs School of Medicine, including Dr. Rob Taylor and Dr. Suzanne Laycock. They really cared for me during the challenging times.

Murphy: This does sound like it does take a village. And it's so wonderful that you've been able to find that sort of support system. Here's our last question and it's one of my favorites to ask. As our listeners may know, the AMA Research Challenge winner is presented a $10,000 grand prize presented by Laurel Road. Let's say you are that winner, what would you do with that prize money?

Chaudhry: So medical school is very expensive. I think that I'll be using the funds to fund the rest of my medical education, including paying for USMLE exams and applying for residency programs.

Murphy: Of course, that's a very practical response. And for our listeners, this has been wonderful to hear about your research. Thank you so much for sharing your work with us today, Kanita.

Chaudhry: Thank you so much for having me.

Murphy: Remember to tune in to the finals of the AMA Research Challenge on December 7, to see Kanita and four other finalists present their work to a panel of expert judges for the chance to win that grand prize. This has been Making the Rounds, a podcast by the American Medical Association. I am AMA Senior News Writer, Brendan Murphy. Thank you for listening.

Cabrera-Sánchez: Join us on December 7 at 7 P.M., Central time to see all 5 finalists present their research to an elite panel of judges. The overall winner will receive a ten-thousand-dollar grand prize—sponsored by Laurel Road.  For full details, visit ama-assn.org/research22.


Disclaimer: The viewpoints expressed in this podcast are those of the participants and/or do not necessarily reflect the views and policies of the AMA.

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