What's Next for Brain Cancer Treatment?

There are many advances on the horizon that will change the trajectory of brain cancer treatment, according to David Reardon, M.D., and Patrick Y. Wen, M.D., both directors of the Center for Neuro-Oncology at the Dana-Farber Cancer Institute in Boston.

The two spoke about the current state of brain cancer treatment, as well as new therapies in the works during a recent Facebook live webinar.

“There’s a whole variety of possibilities,” Wen said, referring to the number of different clinical trials happening at Dana-Farber exploring therapies such as immunotherapy and molecular-targeted therapy. “The goal of the trials is to hopefully find better treatment for the patients.”

Immunotherapy

On the immunotherapy front, researchers are examining the effects of immunotherapy agents such as Opdivo (nivolumab) and Yervoy (ipilimumab) both alone and in combination for patients with glioblastoma — something that Reardon called a major area of focus at Dana-Farber.

“We know cancers have many adaptive mechanisms in place for self-preservation, including strategies they use to hide themselves from the immune system so that our body’s natural defenses don’t realize they’re there or simply can’t effectively attack them. Based on research that has come out in the last few years — some of which has been pioneered here at Dana-Farber — we now are understanding some of the critical mechanisms of cell preservation strategies,” he said.

These agents are typically safer and more well-tolerated with fewer severe side effects than other traditional cancer therapies, such as chemotherapy. Wen is confident that one day there will be the same kind of advances with using immunotherapy to treat brain cancer as there were for lung cancer and melanoma.

Although many of these immunotherapy studies are showing promise across many tumor types, Reardon mentioned that it will likely take much more work to figure out the perfect immunotherapy treatment protocol.

“Unfortunately because of the complexity of these tumors and their defense mechanisms, it’s going to take a lot more research and a lot more effort to identify the optimal immunotherapy drugs and combinations of drugs that will be able to work and utilize this effectively for patients. It’s very complicated,” Reardon said.

Molecular-Targeted Therapies

In recent years, researchers have also become much more proficient in understanding the genetics of brain cancer tumors, mapping out a “genetic blueprint” and identifying unique features of that person’s cancer.

“We now are able to understand the molecular alterations in people’s brain tumors very well. It’s a routine thing we do on all our patients if there’s enough tissue,” Wen said.

The pair agreed that, just like with the use of immunotherapy, it is critical to determine the treatment strategy with targeted agents that works best, be it as single agents or in combination.

Researchers at Dana-Farber are currently investigating therapies that target: IDH, which is one of the most common mutations in grade 1 and grade 2 gliomas; EGFR, which has extra copies appearing in about half of glioblastoma cases; PI3K mutations, which are also common in brain cancers; and OLIG2, a protein with a key role in brain development that, when activated in an abnormal situation, can cause brain cancer to develop.

“We’re getting to the point of personalized precision medicine where we can match the right person up with the right therapy, which I think is a critical strategy,” Reardon added. “We’ve been able to unlock those secrets and mysteries [of cancer cells] and understand them better than before,” Reardon said.