Stromal Cells May Help to Overcome Resistance to Chemotherapy in Patients with Glioblastoma

New research from the University of Pennsylvania shows targeting stromal cells may be an effective way of overcoming resistance to chemotherapy and radiation in patients with glioblastoma (GBM), a deadly brain cancer, according to a study published in Science Translational Medicine.

The researchers found that GBM causes these stromal cells to act like stem cells, naturally resisting attempts to kill them and promoting tumor growth instead. They also identified the pathway that makes cancer vulnerable in a lab setting.

GBM is an aggressive form of brain cancer and the tumors are usually heterogenous or contain different genetic mutations. This means that treatments focused on 1 target are ineffective or only partially effective.

“There have also been few new treatments over the past few decades for GBM, so it’s clear that we need to find a way to make current treatments more effective for these patients,” said study senior author Yi Fan, MD, PhD.

The study focused on overcoming resistance and researchers found that GBM transforms a type of stromal cells, called endothelial cells, so that they act like stem cells. The researchers then found that the resistance is enabled by a signaling pathway called Wnt. The more that Wnt is activated, the more a cell is able to resist treatment like chemotherapy. Previous research has shown that GBM stimulates Wnt activity. Therefore, these findings show the way in which tumors co-opt their environment to survive an attack.

Blocking Wnt signaling may be an effective way to help the cells overcome resistance to treatment. Therefore, the research team used an experimental approach to shut off Wnt signaling in the stromal cells of tumor samples. They found these cancer cells were vulnerable to chemotherapy once the signal was blocked.

The findings support the development of other cells, including cancer. By targeting them, a treatment would effectively get closer to the cause of the tumor’s ability to survive, which may make therapy more efficient, according to the study authors. Additionally, the findings indicate that treatments will remain effective even as the tumor changes.

Reference

• Targeting Stromal Cells May Help Overcome Treatment Resistance in Glioblastoma [news release]. Philadelphia, PA. Penn Medicine News website. Published February 26, 2020. https://www.pennmedicine.org/news/news-releases/2020/february/targeting-stromal-cells-may-help-overcome-treatment-resistance-in-glioblastoma. Accessed March 10, 2020.