Researcher Q&A: Dr. Vashisht Yennu Nanda

Vashisht Yennu Nanda, Ph.D., is an Assistant Professor in the Department of Melanoma Medical Oncology at MD Anderson Cancer Center. Dr. Yennu Nanda is the recipient of an MRA Young Investigator Award and shared a bit about his research for the blog.

How did you get interested in melanoma and your field of research?

It was during my postdoctoral fellowship period, when I found that melanomas were very sensitive to compounds that activate the p53 tumor suppressor by various mechanisms. I was also captivated by the many unknowns in the unique pigmentation-associated pathways that can promote the transformation of normal melanocytes into this aggressive cancer.

YennuNanda, VExplain your research and how it can make a difference for patients.

Over the past decade, treatment of melanoma patients with small-molecule inhibitors that exquisitely target specific oncogenic proteins in melanoma cells have produced groundbreaking responses in most of these patients. However, the responses are not long-lasting and most melanomas eventually become resistant to these inhibitors.

Our research is aimed at figuring out the mechanisms of resistance, and most importantly, developing strategies to counteract them.

What is one thing about melanoma research that surprised you when you first started?

As a grad student and postdoctoral fellow, I worked with many types of cancers, including melanomas, and I was always surprised by the molecular distinctiveness of melanomas compared to all other cancers. Our recent cancer metabolism study results have reinforced this sentiment, as we have found that melanomas are also metabolically distinct compared to other cancers.

How has MRA funding helped your work?

Our research is at a critical juncture of molecularly identifying targeted therapy-resistant melanomas that would best respond to a novel mitochondrial inhibitor, IACS-10759, and systematically evaluating this response. My Young Investigator Award from MRA is supporting this endeavor, which has the potential to make a difference for melanoma patients in the near future.

What do you hope to see more of in the future of melanoma research?

Although giant strides have been made in targeted therapy and immunotherapy of melanoma, resistance is still an issue, and a large number of patients do not respond to immunotherapies. I think the field will benefit from a stronger emphasis on bold fundamental research to understand the molecular changes that occur inside melanocytes and in their immediate vicinity that force these cells to become melanomas in the first place.

Also needed is a strong emphasis on understanding molecular changes in melanomas and their microenvironment during the various stages of metastatic growth, therapeutic response and resistance. Development of novel humanized animal models and a greater patient involvement will be imperative to the success of such research.

What do you do when you’re not conducting research?

Spending time with family and swimming are the two primary activities outside of my research life.

 

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Melanoma and the Problem of Drug Resistance

In 2002, researchers discovered a link between mutated BRAF genes and nearly half of all melanoma tumors. Since then, BRAF inhibitors—drugs that target mutated BRAF—have become a leading go-to weapon in the battle against melanoma. Their job is to cut off signals sent by altered BRAF that promote the rapid growth and division of cancer cells.

BRAF Inhibitors and Drug Resistance

Studies show that BRAF inhibitors shrink melanoma tumors faster and better than chemotherapy. Unfortunately, the treatment’s success is short lived. It only takes about six months for cancer cells to figure out how to use alternate pathways to grow and divide once again.

Eventually, melanoma tumors become resistant to the drug’s effects, rendering the treatment essentially useless. This is similar to how skin, ear and respiratory infections can build up resistance to certain overused antibiotics.

Another problem with BRAF inhibitors is that 20 percent of users go on to develop a different type of skin cancer called squamous cell carcinomas. Although this form of skin cancer isn’t as serious as melanoma, they still require removal and treatment.

Combination Treatments for Melanoma: BRAF and MEK Inhibitors

Studies show that combining BRAF inhibitors with another targeted drug, MEK inhibitors, leads to better results.

You might be most familiar with the success of combination therapies to treat AIDS. Over the past two decades, the introduction of a triple cocktail—a combination of three gene-inhibiting drugs—has changed AIDS from being a deadly disease to making it more of a chronic, manageable condition. One goal with melanoma research is to come up with a combination drug therapy that works as well on melanoma.

How are Researchers Combating Drug Resistance?

The Melanoma Research Alliance is helping to fund many of these research projects in the hopes of finding better treatment options with improved outcomes.

  • Several ongoing clinical trials are exploring new drugs and drug combinations.
  • Other studies are looking into whether taking medications intermittently instead of daily might lower the risk of drug resistance.
  • Laboratory tests and clinical trials explore whether drug treatment should continue once cancer progresses to a certain point. Some studies suggest there may be benefits of continuing drug therapy, while other findings suggest otherwise.

Another innovative therapy now available for melanoma is immunotherapy. With this treatment, medications called immune checkpoint inhibitors stimulate the immune system to recognize and destroy cancer cells more effectively.

Studies are currently looking at the effectiveness of combining immunotherapy with other treatments, such as targeted therapies. Researchers also are exploring whether it’s best to start immunotherapy early in the treatment process or after the disease progresses.

Read more about research funded by the Melanoma Research Alliance.Some of this information was presented as part of our 7th Annual Scientific Retreat, which was held in February 2015. You can read about MRA’s Scientific Retreat.