Cleveland Clinic Lerner Research Institute Leads Study Identifying New Drug Target for Glioblastoma

Cleveland Clinic Lerner Research Institute Leads Study Identifying New Drug Target for Glioblastoma

An international study of glioblastoma led by the Lerner Research Institute of Cleveland Clinic has identified a new drug target for treating glioblastoma. This target is part of a never-before defined cellular pathway found to contribute to the spread and proliferation of a dangerous subset of cancer cells known as glioma stem cells.

More Clarity

Previous research showed that a protein known as FGF2 (fibroblast growth factor 2) upon activation (e.g. turned on) contributes to glioma stem cell self-renewal and tumor growth; however, it was not understood how or why. Now a study led by Justin Lathia, PhD, Cleveland Clinic Lerner Research Institute, identifies FGF2 as an important intermediary in a multi-step, pro-cancer signaling loop and suggests that “turning off” FGF2 may inhibit or even halt the growth and spread of glioblastoma. The results of this study were published in Cancer Discovery.

A First but a Desperate Situation

This study represents a first in identifying FGF2 as a novel druggable target for glioblastoma, the most common primary malignant brain tumor. With standard treatment, the median survival for adults with glioblastoma is only between 11 and 15 months, and recurrence is very common. There is a desperate need for therapies.

The Breakthrough: A Protein called ADAMDEC1

As it turns out, ADAMDEC1 (a disintegrin and metalloproteinase domain-like protein decysin 1)—secreted by glioma stem cells—breaks down what is known as ECM or extracellular matrix, which is a network of molecules that—like brick and mortar—help to hold and anchor nearby cells together. In this protein’s absence, cancer cells can access key nutrients for their growth. One such nutrient is FGF2—the researchers revealed that ADAMDEC1 activates FGF2, which is found within the tumor environment. Like a lock and key, the “turned on” FGF2 selectively binds to and activates a receptor found on the surface of the glioma stem cells called FGFR1 (FGF receptor 1).

FGFR1 Key for Glioblastoma

FGFR1 plays two key roles to drive glioblastoma, including 1) it helps mediate the hallmark pro-cancer characteristics of glioma stem cells including their ability to self-renew and spread, and 2) signals and ultimately induces the expression of ADAMDEC 1—sending this whole cellular feedback loop into motion again.

Research Comment

Dr. Lathia noted that these findings show us that the identified “pathway shows that glioma stem cells’ ability to access key nutrients in their surrounding microenvironment, by way of ADAMDEC1, is integral for their maintenance and spread. Finding a way to interrupt this feedback loop will be important for treating glioblastoma.” 

Call to Action: The study suggests that therapeutically targeting FGF2 may be the key to interrupting the cancer-driving loop. Any feedback from TrialSite News readers?