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Understanding how metabolic defects that cause brain and blood cancers may help in fight to better treat, detect diseases earlier

4803-mallette-frederick-antoineTFRI New Investigator Dr. Frédérick Mallette is breaking new ground in his efforts to characterize metabolic defects associated with brain cancer and leukemia, paving the way for new approaches to treat and diagnose these often-fatal diseases.

Aberrations in two proteins called IDH and IDH2 are often observed in brain and blood cancers. This causes an increase in production of a cancer-associated “oncometabolite” known as 2-hydroxyglutarate (2HG), which in turn may contribute to cancer development. Dr. Mallette’s team was the first to discover how this “oncometabolite” stimulates loss of cellular growth control, which leads to cancer.

“We are working very hard to define the molecular link between metabolic defects and cancer development,” said Dr. Mallette, assistant professor at Université de Montreal.  

“The bottom line is to understand how altered use of nutrients by cells promotes tumor formation, such that we could ultimately find therapeutic targets to prevent unrestrained cell growth.”

His team is using state-of-the-art technologies to analyze DNA in order to identify new functions for IDH1/2 mutations, as well as new biomarkers associated with brain cancer and leukemia for earlier detection.

 “If we can better understand how the metabolite is triggering cancer, perhaps we can find novel avenues to block cancer progression,” he added. “That would be the best-case scenario, and I’m pretty confident we should be able to achieve that goal.”

McGill University researcher Dr. Vincent Giguère leads TFRI’s Montreal-based oncometabolism program project grant team, the sponsoring project for this NI award.

“Members of our program are all extremely confident that Fred Mallette will thrive in our research environment. His complementary expertise in this topic of cancer research will be an interesting asset for our team, and benefit our funded Terry Fox Program,” remarked Dr. Giguère, his mentor.

“My expertise is mainly epigenetics, and now we’ll linking it to metabolism with their help,” agreed Dr. Mallette.

“That’s the cool part, it’s the merging of two different research topics. Together with Dr. Giguere’s group we can perform cutting edge experiments towards understanding how metabolism regulates cancer development – it’s very exciting!”

Project Title: Deciphering the oncogenic properties of cancer-associated IDH1/2 mutations
Award: $450,000 over three years
Mentoring Program: Terry Fox New Frontiers Program Project Grant in Oncometabolism and the Molecular Pathways that Fuel Cancer (2015-2019)

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