Brian L. Schmidt, DDS, MD, PhD
Brian L. Schmidt, DDS, MD, PhD, is a specialist in head and neck cancers whose research focus includes an exploration of the biological and molecular mechanisms of pain related to cancer and associated treatments.
He is the director of the New York University (NYU) Oral Cancer Center and of the Bluestone Center for Clinical Research, and a professor of oral and maxillofacial surgery at the NYU School of Dentistry. In June 2016, the National Institutes of Health awarded Schmidt and colleagues a $1.2 million grant to study gene therapy for the treatment of patients with oral cancer pain.
Schmidt talked to OncLive
about the difficulties of studying cancer pain and developing new drugs.
OncLive: How has our understanding of the mechanisms of cancer pain changed in the past decade?
: The field was developed probably in about 1999. That’s the first publication that I’m aware of that looked at mechanisms in terms of using preclinical models, and by that I mean animal models. Before that time we really had no understanding of basic mechanisms, so there’s been significant advancement over the last 10 years.
Could you briefly describe our current understanding of how cancer pain develops?
Let me tell you what it’s not, because I think that’s important. For many years, people were writing about it but we weren’t testing the possible mechanisms, and what people were writing turned out probably not to be true.
It was initially thought that the pain was due to the cancers growing and pressing on the nerves and we clearly don’t think that’s the underlying mechanism now. Possibly in some cancers that plays a role, but this whole idea of “pressing” really doesn’t work because it’s pretty hard to compress a nerve and there are actually a number of tumors that are not cancer that can compress nerves and those don’t hurt.
There might be a circumstance, for example, if you had a cancer in a perfect location, either let’s say in your leg where the femoral nerve is, or in the paravertebral skeleton where you have what are called spinal roots. In these cases, the cancer could press on the nerve and it would hurt, but that’s probably not a common mechanism.
Probably the best explanation for cancer pain we have is that the cancers produce a number of different molecules—and that depends on the type of cancer—that sensitize the nerves, which makes them respond to stimuli that’s normally not painful. And so the nerves that are surrounding the cancer become fragile, for lack of a better term, and those nerves fire in response to minimal stimuli.
What is the most effective therapy currently available?
I can tell you what’s most commonly used and its effectiveness is highly variable. We’re basically using the same drugs that have been used for thousands of years for pain, which are the opioids. So the narcotics—morphine, fentanyl, methadone, oxycodone, hydrocodone—that entire class of drugs. That’s what’s most commonly used.
Have researchers made any headway in developing drugs that target the underlying causes of cancer pain?
No, they haven’t. Probably the biggest development, and it’s not really targeted therapy, but the biggest development has been for cancers that go to the bone. Those include breast cancer, prostate cancer, multiple myeloma, lung cancer—those cancers go to the bone and cause a lot of bone pain.
We started using a class of drugs called bisphos phonates, which inhibit the cells that break down bone. They specifically inhibit a cell type called osteoclasts. Those drugs work for some patients who have bone metastasis. But we have not discovered true targeted therapies, and one of the challenges has been that the same obstacle that is present for oncologists treating the cancer has also proved an issue for pain physicians, which is that these cancers all behave differently, even within a specific type of cancer, so one colon cancer doesn’t behave like another one, for example.