U of L researchers studying cells in glioblastoma
RESEARCHERS STUDYING HOW BRAIN CANCER CELLS BYPASS CELL-DEATH PATHWAYS
Brain cancer is one of today’s most aggressive, incurable diseases. But now the findings of a University of Lethbridge cancer research team, being shared worldwide, may lead to better outcomes. Glioblastoma (GBM), the brain cancer that killed Gord Downie of The Tragically Hip and former American senator John McCain, has a dismal prognosis and survival rate.
“The median survival rate is about 15 months, even after chemotherapy, surgical removal of the tumour and radiation therapy,” says Lethbridge researcher Nehal Thakor.
“We are trying to understand how these cancer cells bypass cell-death pathways.”
Cell death is a normal and controlled part of their growth and development. But in glioblastoma, cancer cells evade death — even after treatment — and they continue to multiply in an uncontrolled fashion.
Thakor, a professor in the chemistry and biochemistry department at U of L, is also the Campus Alberta Innovation Program Chair of Synthetic Biology and RNA-based Systems.
He’s leading a team that is focusing on mRNA (messenger RNA) and the factors that regulate how it’s involved in cell survival mechanisms. Messenger RNA carries genetic information from DNA to the ribosome, the part of the cell in charge of protein synthesis that allows important bodily functions to be carried out.
In research accepted for publication this spring, Thakor and his team explain that they are looking into eukaryotic initiation factor 5B, described as a protein involved “in the accurate initiation of translation from mRNA to protein.”
“What we’re really trying to understand is how these cancer cells are so good at surviving when they’re not supposed to,” says researcher Joe Ross, a post-doctoral fellow in Thakor’s lab.
“Why are they so good at surviving chemotherapy and radiation? It turns out that one of the things they’re really good at doing is translating proteins and the wrong types of proteins when they’re not supposed to.”
Master’s student Kamiko Bressler, also part of the seven-member team, explains the 5B protein has been shown to play an important role in “normal translation.”
“But when cancer cells hijack normal processes and make them do abnormal things or make too much of certain proteins, that can cause the cells to evade . . . programmed cell death.”
“Glioblastoma is especially good at that, which is why it’s so hard to treat.”
The U of L findings are about to be published for peer review in the research journal Cell Death & Disease. Their study is titled “Eukaryotic initiation factor 5B (eIF5B) provides a critical cell survival switch to glioblastoma cells via regulation of apoptosis.”
Currently, the team is working with braintumour stem cells to see if the cancer cells will grow in the absence of the 5B protein, or if they become more sensitized to therapeutic interventions. These stem cells are the main cause of relapse.
Says Thakor, “If we can target eIF5B using a small molecular compound, then we can treat not only glioblastoma but other types of cancer that have similar mechanisms in place.”
“This proof-of-concept project has the potential to decode information related to the clinical management of GBM, and will have an important beneficial impact on the health of Canadians.”
Follow @DMabellHerald on Twitter