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Manitoba awarded its first TFRI New Investigator

Biologist will use ‘quick-to-clinic’ approach to tackle deadly brain cancer

SachinDNA repair biologist Dr. Sachin Katyal has been awarded Manitoba’s first TFRI New Investigator Award for his quick-to-clinic personalized medicine approach to better treat patients with the incurable brain cancer glioblastoma multiforme (GBM).

“Everyone’s so excited Manitoba has won a Terry Fox Research Institute award, especially because this province was Terry’s birthplace,” says Dr. Katyal, based at Cancer Care Manitoba and the University of Manitoba. “Glioblastoma is a pretty insidious disease and is almost like a death sentence -- it’s got fairly grim statistics, and my goal is to change that.”

More than 2,500 Canadians are diagnosed with brain cancer each year, and GBM is the most common -- and aggressive tumour. Average life expectancy after diagnosis is just 15 months, and fewer than 5 per cent of patients live beyond five years. [Note: In October 2017, Tragically Hip band member Gord Downie died of this disease.]

“The biggest problem with GBM is no matter what you do in terms of treatment – whether it’s radiation, chemotherapy, surgery – that tumour comes back,” says Dr. Katyal. “And when it returns, it comes roaring back and it’s not sensitive to your typical treatments anymore.”

Treatment options such as chemotherapy and radiation essentially work as DNA-damaging agents towards cancer cells. Tumours, however, hijack this process and put DNA repair into overdrive, which allows them to fix damage faster than normal cells in the body. When chemo and radiation injure cancer cells they are consequently repaired quicker than ever – a process that leads to tumour resistance and aggressive recurrence.

To counter this, Dr. Katyal is analyzing resistant tumour cells to determine what DNA-damaging enzyme repair proteins are allowing cancer cells to survive. He has also developed a high-throughput DNA damage repair suite and will use this as a drug-screening platform. Results will be compared against the FDA-approved drug library to see if existing therapies could be used to inhibit DNA repair fidelity, enhance sensitivity or damage resistant glioblastoma cells.

“It’s what we call a ‘quick-to-clinic’ personalized medicine approach,” Dr. Katyal says, noting his mentor, neurosurgeon Dr. Sheila Singh (McMaster University), will be able to bring potential new treatment options to her patients. “It’s not going to help every patient, but it has the potential to help some, and to make a difference in the lives of GBM patients.”

Dr. Singh leads one of TFRI’s newly funded PPGs on glioblastoma and is a former NI award holder (2011). “Sachin has tremendous opportunity and potential to dramatically alter the DNA- damage repair research landscape and to make a meaningful impact for patients stricken with GBM,” says Dr. Singh. “I am thrilled about the formation of this new collaborative relationship and I consider myself privileged to support Dr. Katyal’s professional development and research program.”

At the end of his three-year award, Dr. Katyal hopes to have brought new hope to glioblastoma patients. “I want to erase the stigma associated with GBM, and create new advancements and new hope,” he says.

Project Title: Targeting resistant glioblastoma multiforme (rGBM) through suppression of overactive DNA repair activity

Award: $450,000 over three years

Mentoring Program: Targeting clonal heterogeneity in treatment-refractory glioblastoma with novel and empiric immunotherapies

 

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