New brain cancer treatment strategy developed at Virginia Tech’s Fralin Biomedical Research Institute
ROANOKE, Va. (WDBJ) - Researchers at Virginia Tech’s Fralin Biomedical Research Institute at VTC have developed a new way to treat glioblastoma, an aggressive brain cancer with an average survival time of approximately 15 months. Their findings published this week in Oncogenesis, according to the university.
“By using a combinational therapeutic strategy, we’ve created a promising approach to combat chemoresistance in the most lethal brain cancer,” said Zhi Sheng, assistant professor at the Fralin Biomedical Research Institute, who led the study.
Glioblastoma usually resists chemotherapies, including temozolomide, a drug that damages DNA and causes tumor cell death. Nearly half of glioblastoma patients resist the treatment by producing a DNA-repairing enzyme, MGMT, but until recently it wasn’t clear why temozolomide wasn’t working for patients who lacked the MGMT enzyme.
Sheng’s research team used glioblastoma cell lines and primary glioblastoma cells derived from patient tumor specimens to find inhibiting two specific proteins when combined with temozolomide, produced an effective “triple combinational therapy” which beat chemoresistance. The findings could significantly delay tumor recurrence resulting from chemoresistance and prolong survival in glioblastoma patients, according to Sheng.
“Further studies are needed, but this may be the kill switch for glioblastoma that we’ve been searching for – a potential way to prolong cancer survival time with strong translational potential,” , the study’s co-corresponding author.
In older studies of gliomas, increased levels of connexin 43 protein overpower tumor growth. But in more aggressive glioblastomas, Sheng’s research team showed that more connexin-43 inversely promotes cancer growth and chemoresistance.
The researchers described the positive effects of inhibiting connexin 43 activity in their 2015 study. They found the right target, but their studies in canine glioma patients revealed difficulties in delivery of effective alphaCT1 doses to brain tumors in companion animals.
“If we’re successful in translating this discovery, we will have a chance to overcome drug resistance in glioblastomas expressing high levels of connexin 43 and PIK3CB/p110beta, which account for 25 percent of all cases,” Sheng said.
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