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New Prospects for Treating Brain Cancers

Melanie Cole (Host):  If you are someone who has been diagnosed with a brain tumor, what are the potential treatments for patients and what can you expect as an outcome? My guest is Dr. Benjamin Purow. He is a neurologist who specializes in researching new brain tumor treatments and caring for patients with brain tumors. Welcome to the show, Dr. Purow. Tell us a little bit about brain tumors and some of the challenges of developing treatments for patients with brain cancer.

Dr. Benjamin Purow (Guest):  Sure. I am happy to. Brain tumors can present in lots of different ways. That is something that people are often curious about, that they worry about. It can present as something like a severe headache, but in most cases by far, headaches are due to other things. Seizures are very common presenting symptom. Those can be much more diverse than people expect. Those can be the grand mal seizure that people are used to hearing about, but also much more subtle things that are very brief, difficulty with speech or numbness or tingling somewhere, sometimes difficulty, weakness somewhere or balance. There really are a plethora of symptoms and it is always good to consult with your doctor. There are a number of challenges once you have diagnosed a brain tumor and typically that happens after patients present with some of the symptoms I have described or one of the symptoms I have described. It usually leads to an MRI, scan of the brain, and these are extremely sensitive scans that can show us these brain tumors. From there, we typically need a neurosurgical colleague to take some of this tissue and we will go on to some of the existing treatments such as initial surgery, radiation, chemotherapy. Unfortunately, for some of these brain cancers, and I will mention one in particular called glioblastoma or GBM for short, that is the most common and most aggressive kind of brain cancer we see in adults and we can see it in children as well. Some of the challenges for that cancer, as well as for some of the other brain tumors that are out there, include invasiveness into critical structures of brain. If they stay as a discrete lump, very often the neurosurgeons can just take that lump out. Unfortunately, glioblastoma and other brain cancers invade elsewhere into the brain. They are fairly resistant to existing treatments such as chemotherapy and radiation. There are a fairly diverse group of tumors. They can be heterogeneous and, worst of all, very adaptable to a lot, if not all, of the existing treatments that we have. They can always evolve and find a way around these treatments. There is also something called the blood-brain barrier, which makes it hard to get some of the treatments that we give intravenously get them into the brain. There is kind of a tight barrier between our blood and our brain itself, where these tumors are lurking.

Melanie:  Describe for us some of the research that you are working on right now. 

Dr. Purow:  Sure. We are excited about a number of things that we are doing in the laboratory right now. I mentioned the adaptability of this cancer. One of the things that we and others in the field are trying to do is tackle these cancers on multiple fronts all at once with one or two therapies at a time. We really need good multi-targeted therapies. We have some work in the lab focusing on what is essentially a genetic approach using very small molecules called microRNAs. There are actually lots and lots of these found normally in our self, but cancers such as glioblastoma and other brain cancers tend to suppress or increase expression of some of these, and some of these microRNAs that are down-regulated in the cancers are actually pretty toxic to cancers if we can go back and deliver them to glioblastoma and other cancers. One of the things we focus on in the lab is exploring these microRNAs, their biology, but also trying to use their delivery as therapy for brain cancers, given that each of these microRNAs can target multiple pathways at once. They tend to suppress their targets and a given microRNA can hit lots of these pathways that are very important in these cancers. We also have another big project in the lab, looking at a fairly new target in glioblastoma, brain cancers, and actually cancer in general. It is a protein called diacylglycerol kinase alpha or DGK-alpha. We think it is a very nice signaling hub in these cancers, such that when we inhibit this, we can actually attack multiple cancer pathways all at once. It got some other exciting aspects that seem to directly kill the cancer cells when we inhibit these. It also attacks their blood supply, may also boost the immune system, so exciting at multiple levels. We also have some new projects in the lab, basically a personalized medicine approach. We are trying to move forward where we can target subsets or subtypes of glioblastoma and other brain cancers. We are also exploring what we hope are some smarter, more rational combinations of some of the existing drugs that are out there.

Melanie:  Wow! How exciting is this research you’re doing now. Tell us a little bit about how long some of these things when you talk about the DGK-alpha and these microRNAs, what can patients expect? When are you going to know if these can be used on patients and how long? What is the future of brain cancer care? 

Dr. Purow:  Sure, that’s a great question. With some of these research fronts that we are working on, it will probably take years to develop. The microRNAs, in particular, there is a major delivery hurdle and we and others are working on overcoming this. There’s some [treading] progress being made there. The DGK-alpha project, it may actually not be that long because we found that there is an old drug that was being used for a different purpose in some clinical trials, not yet FDA-approved, but were safe in clinical trials being used for something else. We find that we can repurpose that drug as an inhibitor of DGK-alpha. We think that is going to really speed up clinical trial of this approach in the not-so-distant future in the next year or two with inhibition of DGK-alpha. With some of our other projects, we are actually using existing drugs that already are being used for cancer or repurposing existing drugs in new ways to use them against brain tumors and other cancers and that’s going to let us go to the clinic much faster. Truly an exciting time more broadly with lots of great new developments for cancer in general and that really extends also to neural oncology to brain cancers. I think we will for a long time be using chemotherapy, although hopefully more gentle ways than is typically thought of, and radiation as well. I think we are getting toward better use of targeted agents. Some of these are more sophisticated, personalized medicine or re-matching the drugs better to the patients who are out there. We will also be doing, I think, better combinations of existing drugs. One of the most exciting areas out there is with immunotherapy, boosting the immune system against cancer, including brain cancer. We used to think that it might not apply to brain tumors, but they really seem to be applicable to glioblastomas and these other awful brain tumors. There was a recent meeting in November in our field, the biggest brain cancer meeting there is, and there were some very exciting new clinical trial results with one immunotherapy. There are some other immunotherapies that looked great. These are kind of nice because they are not very toxic often and they really use your own immune system to fight the cancer. This meeting was also exciting because there were positive results with the really quite an interesting alternative approach to fighting cancer, applying electrical currents to the head against the tumor and that had positive results. So there are lots and lots of exciting things going on right now in this field and throughout oncology actually.

Melanie:  Wow, Dr. Purow. Why should patients come to UVA for brain cancer care, if anything else, than just to see you and hear your enthusiasm for the subject? 

Dr. Purow:  I think there are lots of reasons why I would encourage patients to see us. We see very many patients who have brain tumors. We have broad experience. We give everyone that we see really the state-of-the-art care, but then we go beyond and really try to go the extra mile. We give compassion to all the patients that we see. We really treat every patient the way that we would want ourselves or a family member to be treated. It is a frequent question from patients. What would you do? How will you want to be treated at this point? I really give the same answer, which is just “I already was talking to you about exactly what I would want to do.” I think we really apply the golden rule or, if you will, the platinum rule, to do for people what we would want for ourselves and our loved ones. We also have here a number of clinical trials in any given point and that is applying, trying things that are in the pipeline to our patients with these brain tumors, glioblastoma, and other brain tumors. Even outside of the clinical trials, though, we have the willingness to, as I said, do the standard of care and beyond, really look for combinations of standard of care with other existing agents that might give a little boost to the therapy, if we have to add on a blood pressure medicine or a seizure medicine for a patient. We are always thinking about medicines that will not only do that function that we need, but pick one that may also give a little boost against the brain cancer. Some of our patients want cocktails, state-of-the-art and other things, and we are very happy to fight as best we can and make those cocktails for our patients. We emphasize not just length of life but also quality of life, and that is really paramount in something that we are always thinking about. 

Melanie:  Thank you so very much. Really, really great information and very exciting research. You are listening to UVA Health Systems Radio. For more information, you can go to uvahealth.com. That’s uvahealth.com. This is Melanie Cole. Thanks so much for listening.