High Grade Gliomas (HGGs) are a class of brain tumors with poor prognosis. Despite being heterogeneous, all HGGs are treated in the same fashion, with surgical removal followed by chemo- and radiation therapy, and they invariably recur. Implicated in tumor resistance to radiation therapy is the DNA damage response, the cell’s process for repairing radiation-induced DNA damage. This repair process can allow tumor cells to escape the treatment and continue to grow. The signaling molecule TGF-β activates the DNA damage response, and inhibitors of TGF-β signaling can prevent this. Examination of tumor samples indicates that TGF-β signaling activity is variable in HGGs. Inhibitors of the TGF-β pathway are currently being tested in clinical trials for their ability to delay tumor cell growth. However, variability in TGF-β signaling suggests that some HGGs may respond to TGF-β inhibition better than others. Now, research from the labs of Dimitris Placantonakis and Mary Helen Barcellos-Hoff, at the New York University School of Medicine, shows a potential approach to personalize treatment for HGG by using TGF-β inhibitors to modulate the DNA damage response. By growing HGG explants, small samples of tumors that preserve the tumor microenvironment, in the lab, the groups showed the ability of TGF-β inhibition to prevent both radiation-induced DNA damage repair and increased expression of cancer stem cell markers. This radiosensitivity can be measured relatively quickly and easily. With such knowledge, clinicians can examine a given patient’s tumor and determine if TGF-β inhibition is effective as a radiosensitizer that would render residual tumor cells more susceptible to radiotherapy. This would enable the clinicians to personalize the therapy to the patient’s tumor, and with further study, this may lead to improved outcomes for HGG patients. This work was supported by a NYSTEM institutional training award, C026880, to NYU.
Bayin NS, Ma L, Thomas C, Baitalmal R, Sure A, Fansiwala K, Bustoros M, Golfinos JG, Pacione D, Snuderl M, Zagzag D, Barcellos-Hoff MH, Placantonakis D. Patient-Specific Screening Using High-Grade Glioma Explants to Determine Potential Radiosensitization by a TGF-β Small Molecule Inhibitor. Neoplasia. 2016 Dec: 18(12): 795-805.