Additional Inhibitor May Enhance Efficacy of Common Therapy in Combatting Glioblastoma

Adding an inhibitor to anti-vascular endothelial growth factor (VEGF) therapies may be able to enhance the treatment’s efficacy and help overcome resistance in glioblastoma, an aggressive form of brain cancer, according to a new study published in Nature Communications.

There will be approximately 24,000 diagnoses of malignant glioblastoma in the United States in 2018, according to the American Cancer Society. The disease is the most common and most aggressive primary brain tumor, with a median survival of approximately 14 months.

The use of anti-VEGF therapies is a common treatment approach for malignant cancers such as glioblastoma, involving drugs that target VEGF, a signaling protein that stimulates the formation of blood vessels. However, tumors can be highly resistant to anti-VEGF therapies alone.

The study aimed to determine whether pairing anti-VEGF therapy with another currently available drug could make tumors more sensitive to treatment and prevent resistance. The researchers analyzed human glioblastoma specimens and found VEGF receptor expression was reduced in tumor-associated endothelial cells. They found that blocking the platelet-derived growth factor (PDGF) pathway prevented the transformation of tumor endothelial cells, which induces resistance to therapy, thus establishing PDGF as a potential treatment target.

Overall, the findings suggest that adding PDGF inhibitors to treatment with anti-VEGF therapies can help promote sensitivity to the treatment and increase its efficacy, the researchers noted.

“This could be key to solving the biggest problem in the field of anti-vascular cancer therapies,” senior author Yi Fan, MD, PhD, an assistant professor of Radiation Oncology at the Perelman School of Medicine, University of Pennsylvania, said in a press release.

To test the combination therapy, the researchers used a genetically engineered glioblastoma mouse model. According to the results, blocking both VGEF and PDGT improved overall survival in the mice.

“These findings point the way toward a next generation of anti-VEGF therapies, opening the door to version 2.0,” Dr Fan said.

Further research is needed to evaluate the combination in humans, but the findings offer exciting opportunities to treat malignant cancer, the study concluded.

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References

Liu T, Ma W, Xu H, et al. PDGF-mediated mesenchymal transformation renders endothelial resistance to anti-VEGF treatment in glioblastoma. Nature Communications. 2018. https://www.nature.com/articles/s41467-018-05982-z#Abs1

Additional Inhibitor Can Help Anti-VEGF Therapy Overcome Resistance in Deadly Brain Cancer [news release]. Penn Medicine’s website. https://www.pennmedicine.org/news/news-releases/2018/august/additional-inhibitor-can-help-anti-vegf-therapy-overcome-resistance-in-deadly-brain-cancer. Accessed August 27, 2018.