Soma Sengupta, MD, Neuro-oncologist, Associate Professor in Neurology and Rehabilitation Medicine, Associate Director of the University of Cincinnati Gardner Neuroscience Institute Brain Tumor Center, and Harold C. Schott Endowed Chair of Molecular Therapeutics, talks about a new treatment for melanoma.
When someone is diagnosed with advanced melanoma, do they have a lot of treatment options?
SENGUPTA: Melanoma has been one of the cancers where there has been targeted treatments and immunotherapy in use. The problem is not everybody responds to it because you have to have specific mutations for the targeted treatments to work, and only a subset of patients responds to the immunotherapy.
So, with that in mind, what have you and your colleagues been looking at?
SENGUPTA: The journey started in Boston. I was very interested in how to make existing drugs better or how to make immunotherapies work better. We found a compound that increases the ability of the immunotherapy to work and increases the ability of radiation to work. Why is this important? Melanoma eventually tends to go to the brain, and we need drugs that can go into the brain space easily. We also need drugs that don’t cause toxicity to the bone marrow and are tolerated well. If you combine them with an immunotherapy, it makes the immunotherapy more effective.
Is this a drug that crosses that blood-brain barrier?
SENGUPTA: Yes. This class of compound belongs to the benzodiazepines, the most famous one being Valium. Valium had very poor publicity because it became addictive to some people because it was being prescribed in a way that it shouldn’t have been. But the thing that Valium does and the reason why it had this addictive potential is that it gets into the brain. This compound is like Valium but targets the receptor in cancer cells. It’s not as addictive as the parent compound, so people can’t really get a buzz from it, but it does make the cancer cells more sensitive to radiation and more sensitive to immunotherapy.
Is this a drug that was used for anxiety that you’re looking at repurposing? Is that a correct way to put it?
SENGUPTA: No. It’s a new compound based on its parent. A repurposed drug would be if we took Valium and used it. We did try that to see if the cancer cells would respond to Valium, but you would need a lot of Valium for that to work. This drug is more specific for the type of receptor in the cancer cells. So, although it’s related to the parent compound, it’s different. Because it’s different, it would need to be FDA approved. We have done studies in mice, and the groups before have looked at it in another setting and even rhesus monkeys. So, we know that it’s not toxic in these animal models. The next step for us would be to get the compound FDA approved which is easier said than done because that requires a lot of paperwork and a lot of experimental work. Once it’s been approved by the FDA and we have what’s called an IND in place, we can then start using the compound in clinical trials.
How far away from clinical trial is this compound?
SENGUPTA: It depends on how we can get the compound approved by the FDA. We’re applying for funding through NIH mechanisms to help us fund this.
Can you tell me a little more about the compound and what it is and where it’s been studied before?
SENGUPTA: Yes. It’s called QHII066 and was developed by Professor James Cook at the University of Wisconsin, Milwaukee. He is very well-known in developing these group of benzodiazepines. He and his team have done some incredible work where they’ve created compounds for epilepsy to treat epilepsy and make other anxiolytics. So, Professor Cooke and I have been working together from the very beginning. I started working on this receptor and finding its effects when I was at Harvard. At Boston Children’s, I worked for Professor Scott Pomeroy, who’s one of the chiefs of neurology and a neuro-oncologist.
Why is it so important to continue to look at these other drugs and mechanisms for treating advanced cancer?
SENGUPTA: Imagine you’re the patient with the melanoma who is not responding to immunotherapy. What if we could give a drug that’s easily tolerated for the immunotherapy to now work? What if you have melanoma and you have brain metastasis? What if we could make the radiation more effective when those brain metastases are treated? That’s why it’s important to have a drug that can help patients live longer with a better quality of life. The other thing is to have a compound that’s not so expensive that it would cripple the patient in being able to afford such a medication.
How would this potentially be administered? Would it be an oral therapy down the road or would itthis need to be something that would be infused?
SENGUPTA: It can be given as an oral therapy, but the formulation that we’re working on currently is an intravenous one.
Is there anything else you would like people to know?
SENGUPTA: One of the things that might be of interest is, this compound is not only effective in melanoma. We are working in my group that I share with Dr. Pomeranz Krummel on medulloblastoma, which is a pediatric brain cancer. We have collaborators in neuroblastoma, which is another cancer. We have projects in lung cancer that the team is doing, and another in brain cancer called glioblastoma. So, it’s not just a one hit wonder in one cancer. The other thing I do want to also mention is that what we do is part of a team. So, Dan and I couldn’t do what we do without a fantastic group of scientists. One of my members, Laura Kallet, has been with me for a while, as well as Debanjian Patecharia, Camden Danatian, and Gwali Kumar. So, we have an excellent group of PhD level scientists that make it possible.
Interview conducted by Ivanhoe Broadcast News.
END OF INTERVIEW
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