Knocking Out GMB 'Hub' Could Stop Tumor Growth

There may be a new target that can boost the effectiveness of treatment for glioblastoma — a difficult-to-treat brain cancer — according to recent research conducted at The University of Texas MD Anderson Cancer Center.

Essentially, in preclinical study, when fibrinogen-like protein 2 (FGL2) was depleted or “knocked out” in tumor cells, the glioma cells no longer grew, Amy Heimberger, M.D., professor in the Department of Neurosurgery at The University of Texas MD Anderson Cancer Center, said in an interview with CURE.

The FGL2 protein, which has been found to suppress the immune system, was found to be highly expressed in patients with glioblastoma. By “turning off” the protein, researchers may be one step closer to stopping tumor progression.

The secretion of FGL2 from tumor cells stops CD103 dendric cells, which are responsible for activating T cells, which essentially go on to attack cancer cells. Traditionally, glioblastoma does not have a robust T-cell immune response, which is the reason why immunotherapy has not been promising in this field. But Heimberger explained that FGL2 is like a “hub” that not only affects T cells, but also other checkpoints and myeloid suppressor cells.

“For many of the things that can go wrong in this cancer, this is the responsible party, so to speak. This is the gang leader for many of these mechanisms,” she added.

In order for the CD103 dendridic cells to activate the T cells, they must get into the tumor microenvironment, which is located in the patient’s central nervous system (CNS).

“The big deal (of our findings) is that everyone has always thought that the brain is immune-privileged, and that it can’t have immunological recognition,” Heimberger said. “So, this is another paper that is really stating that old understanding of how the immune system is working is wrong.”

However, because this research is only in preclinical stages, its findings are many years away from agents being developed and eventually approved by the Food and Drug Administration.

In the meantime, Heimberger emphasized the importance of patients with glioblastoma seeking treatment advice from providers at a major academic health care setting who frequently deal with this type of brain cancer.

“Patients and their families need to be proactive,” she said. “Ask a lot of questions, go to some of the major centers. The thing that I worry about is that sometimes people are told things like their tumor is inoperable or that nothing can be done, so they’re sent away in a palliative manner without really getting a chance.”

Heimberger added that community oncology centers may not always be up-to-date on the latest research and contemporary treatment strategies. “I’ve seen a lot of patients over the years who have been told, ‘You can’t get surgery,’ and then within a week, we get them on the operating room table,” she said.