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Topics: Clinical & Translational Research, Education & Training, Five Questions

Can Metabolic Reprogramming Starve Thyroid Tumors?

Five Questions with Athanasios Bikas on his training with Harvard Catalyst's Clinical/Translational Research Academy.

Athanasios Bikas with his wife and nephew.
Athanasios Bikas with his wife and nephew.

Athanasios Bikas, MD, PhD, had one of those aha moments early in his medical training that pushed his career path into clinical and translational research. He was assisting in a clinical trial under an early mentor, a leading expert in thyroid cancer. One of the participants had a remarkably positive response to the medication being investigated – it essentially halted the tumor’s growth. Witnessing the patient’s emotive gratitude, Bikas knew he wanted to conduct research that would significantly impact human health.

Today, as a clinical fellow in endocrinology at Mass General Brigham, Bikas is working on new approaches to thyroid cancer that may do just that. He is a 2021 enrollee in Harvard Catalyst’s two-year Clinical/Translational (C/T) Research Academy, which offers advanced training to early-career C/T researchers.

You’re nearing the end of your C/T Research Academy training. How does this intersect with your career as a young investigator and your research goals?

C/T Research Academy has been a very important part of my training here at Harvard Medical School. While I did have research experience before starting my endocrinology fellowship, participating in this training program imparted the core principles of clinical and translational research.

We receive quite a robust education in biostatistics, which is really an essential element in the “ABCs” of research. We also gained insights into how to design and successfully launch clinical trials. I aspire to become a trialist, because it is one way to make a real difference in people’s lives. Now I know some of the problems faced in conducting clinical trials and how to overcome them.

The other thing is the connections. The academy has brought me into talks with leaders in the field and with other young investigators like me who hope to achieve similar goals in their fields. Now we can work together as collaborators.

You’re investigating a potential therapy that would essentially starve tumor cells from the inside out. How does this work advance thyroid cancer treatment?

As a community, we have become more conservative in how we treat thyroid cancer. While the dogma in past decades has been to be treat these cancers aggressively, we have now realized that in many cases less is more. However, we do still need new approaches for fast-growing tumors.

“The academy has brought me into talks with leaders in the field and with other young investigators like me who hope to achieve similar goals in their fields. Now we can work together as collaborators.”

Thyroid cancers are still on the rise, not only as small tumors but also as bigger, more aggressive ones. About 40,000 to 50,000 new cases are diagnosed each year in the United States. It is now the most common cancer found in young adults and adolescents.

To treat those tumors, we should understand how they work. In my primary lab under Iñigo Landa and Erik Alexander, we focus on genomics. We have a few papers examining the role of additional mutations other than the recognized ones, and how these affect tumor prognoses.

But genomics is not the entire story. We also want to focus on the metabolism of these tumors, on how the tumor cells interact with each other and their micro-environment. What is driving changes in metabolism within those cancer cells? If we can gain a better understanding of this, then we will know exactly which pathways to target.

So, we are trying to understand what is happening in metabolic pathways at the molecular and cellular levels and then apply that knowledge to find new treatment options for people with thyroid cancer, especially when it’s aggressive. In the meantime, we hope to also identify new diagnostic approaches.

Your work targets the mitochondria to strangle tumor cells’ energy-production pipelines. Is that a novel pathway for a thyroid cancer drug?

It’s not a new concept in the cancer world–people have been looking at the role of mitochondria in cancer over the last couple of decades–but we are among the first to have published on this topic in relation to thyroid cancer.

Cancer cells usually rely on glycolysis to produce the energy, the ATP, that they need to proliferate. We have shown that thyroid cancer cells are not only using glycolysis but also mitochondria to produce energy for growth via specific proteins, including COX4. In my previous lab under Vasyl Vasko, we focused on repurposing several already FDA-approved compounds–medications like metformin, for example–for the treatment of thyroid cancer.

We’ve studied chlorpromazine, an anti-psychotic medication currently used in psychiatric practice. In a project funded by the American Thyroid Association, we showed that chlorpromazine is a COX4 inhibitor. We then investigated whether it would work in thyroid cancer and found it effective both in vitro and in vivo. We are in the process of publishing those data, which lead us to think that this could potentially be an option for treating medullary thyroid cancer.

How did you get interested in this area of research?

I’m originally from Greece, and my father is an endocrinologist there who specializes in gestational diabetes. Growing up, I would constantly hear about thyroids, adrenals, and diabetes, etc. So when I began medical school, those concepts were not new to me; I was drawn to them. After medical school, I started working towards my PhD in endocrine oncology. My mentors were world experts in thyroid cancer.

“I want to take novel findings in the lab and translate that research back to the people, to my patients, so they can actually benefit from them.”

When it was time to choose a fellowship, I was torn, because both endocrinology and oncology were attractive to me. I chose to be an endocrinologist because I am able to see the entire spectrum of thyroid cancer from the less aggressive to the more aggressive.

I realized pretty early in my training that interacting with patients was important to me. During my fellowship, it became even more clear: I don’t only want to focus on basic research; I want to see patients and make a difference in people’s lives.

I was working in Washington, DC as a research fellow with my mentor at the time, Dr. Kenneth Burman, who was conducting a clinical trial in thyroid cancer. One of his patients with pretty aggressive cancer had a really great response to the medication. His tumor burden stabilized for about a year, and even went down a little. That patient was so appreciative of what my mentor had done for him.

I remember thinking: This is what I want to become in the future. I want to take novel findings in the lab and translate that research back to the people, to my patients, so they can actually benefit from them.

How do you find work/life balance?

My wife is a rheumatologist at Beth Israel Deaconess Medical Center, and we both work long hours. Fun fact: She is also a trainee in the C/T Research Academy, so we see each other at meetings.

Sometimes it’s hard to keep a good work/life balance. However, I think it is very important, because if you don’t do something to take your mind away from work, then you cannot be the best version of yourself at work.

For me, what does it is exercise. I’m trying to be good at basketball, and I try to play soccer. I’m a big sports fan. I play and I watch. We have a group chat with some of my best friends where we talk about the NBA. My wife jokes that I spend more time texting them than her.

But, we manage to spend some quality time together, and she is very supportive. We support each other. I think that’s another major component.

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