Researchers who discovered that an engineered cold sore virus could help destroy brain tumors from the inside out have determined a one-two punch might be the key to finish them off. This virotherapy could make a class of investigational cancer drugs more effective, according to investigators at The University of Texas Health Science Center at Houston (UTHealth).
The research was published today in Clinical Cancer Research, a journal of the American Association for Cancer Research.
Nearly 24,000 people in 2020 will be diagnosed with malignant tumors of the brain or spinal cord and treatment options are limited. Most people diagnosed with a malignant brain tumor do not survive beyond two years.
“Therapeutic viruses are increasingly being used to treat cancer,” said Balveen Kaur, MD, the study’s senior author, professor, and vice chair of research in the Vivian L. Smith Department of Neurosurgery at McGovern Medical School at UTHealth. “One therapeutic virus is approved to treat melanoma, and many others are being investigated for use with other types of cancer. My team researched how these viruses change the biology of the brain tumor that is left behind after virus treatment, and how to leverage that to create strategic therapies that can better eradicate cancer.”
Kaur’s team discovered that cancerous cells treated with an engineered herpes virus send a signal to adjacent cells, making them responsive to a class of investigational drugs, called gamma secretase inhibitors, that can finish off the tumor.
“These cold sore viruses express tiny molecules, called micro-RNA, that activate the NOTCH signaling pathway – a mechanism known to initiate cross-talk between cells. This is the first discovery identifying that this small virus-encoded molecule can ‘ring the doorbell’ on adjacent uninfected tumor cells, educating them to stop resisting the investigational cancer drug.”
In mice models, treatment with the one-two punch of the virus and the cancer drug resulted in a significantly higher improvement in killing the brain tumors, and allowed the animals to live longer than if they had just been administered the virus.
“This study highlights the importance of combining NOTCH pathway-blocking drugs with virotherapy in future research studies to evaluate its safety and efficacy in patients,” said Kaur, John P. and Kathrine G. McGovern Distinguished Chair at the school. “Continued research in this area will be critical to harvest the therapeutic benefit of combining these agents for cancer patients.”
The study was supported by a multi-institutional program project grant from the National Cancer Institute and a research scholar grant from The American Cancer Society.
Co-first authors from McGovern Medical School were Yoshihiro Otani, MD, PhD, a postdoctoral researcher; and Ji Young Yoo, PhD, an assistant professor of neurosurgery. Kaur and Yoo are on the faculty of The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences.
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