Blocking cell-to-cell communication shows efficacy in mouse model of glioblastoma

UF's Loic P. Deleyrolle

An assistant professor of neurosurgery at The University of Florida (UF) College of Medicine has demonstrated the potential of a novel therapeutic strategy to significantly slow the growth of an aggressive brain tumor.

The technique Loic P. Deleyrolle has developed relies on blocking the cell-to-cell communication related to glioblastoma. Deleyrolle said that by cutting off their communications pathway, the deadly cells are sufficiently kept in check, which can improve the survival time by 50% in a mouse model.

The team, which includes Deleyrolle as co-author as well as 8 other UF researchers, targeted a protein called Connexin 46 which is a component of gap junctions--a channel found between most cells but importantly one that is central to glioblastoma growth.

"When we shut down those channels in the cancer stem cells, we can significantly reduce the tumor-forming abilities of the cells," says Deleyrolle.

They published their work in Cell Reports and found that by genetically silencing Connexin 46, mice were protected for up to 100 days. Mice that had the channel protein died within two months.

A DNA-alkylating agent, temozolomide, has long been used in chemotherapy treatment against glioblastoma but is usually used in conjunction with another therapy due to the hosts' prompt resistance to the drug.

Glioblastoma is notorious for its metastasis whether surgical resection, radiotherapy, chemotherapy or a combination of these are used. However, this promising preclinical study may see its way to the clinic soon as all of the current drugs they used are either on the market or in clinical trials.

Despite the high mortality of the brain tumor, Deleyrolle remains optimistic about their new findings: "Any significant increase in survival time will be a meaningful improvement because current treatments provide only weeks of efficacy."

The researchers are currently seeking a new federal grant in order to roll out clinical trials. Gap junction proteins like Connexin 46 may be prove to be a novel target, at least in combination with other chemotherapies used against the deadly cancer.

- here's the release

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