New Drug Shows Promise Slowing Tumour Growth in Some Hard-to-Treat Cancers
Research, Partnerships
Photo courtesy of Sinai Health
Professor Daniel Durocher
By
Amanda Ferguson
Scientists at Sinai Health and the University of Toronto say a new drug designed to block an enzyme essential for the survival of certain cancer cells shows promise in curbing tumour growth.
The researchers identified genes that are essential for the viability of CCNE1 amplified cancer cells, which are characteristic of some hard-to-treat ovarian, endometrial and bladder cancers.
The team found the enzyme PKMYT1 is essential in CCNE1 amplified cells, but not in otherwise healthy cells. In collaboration with precision oncology company Repare Therapeutics, the team developed a drug called RP-6306, which blocks PKMYT1 activity and effectively kills the cancer cell.
“These cancer cells depend on the PKMYT1 enzyme to survive,” said Durocher. “Our preclinical data show enormous promise in the drug RP-6306’s ability to target these types of tumours and profoundly inhibit tumour growth.”
Currently, tumors with CCNE1 amplification have very few therapeutic options. David Gallo, a senior scientist at Repare Therapeutics, said they’ve been able to demonstrate that RP-6306 is both potent and selective for oral use in humans.
“Gynecological and other solid tumours with amplifications of CCNE1 are notoriously resistant to current standard-of-care treatments,” said Gallo, co-first author on the Nature paper. “There is a dire need to find new options for these patients.”
The work was a close collaboration between the Durocher lab and Repare Therapeutics. Durocher founded Repare Therapeutics in 2016 alongside Frank Sicheri, also an LTRI senior investigator who is a professor of molecular genetics and biochemistry at U of T.
The company is built on the concept of synthetic lethality, a process that incorporates functional genomics to discover genetic vulnerabilities to specific cancer mutations.
“This close collaboration between our group and Repare highlights how industry and academia can work together to discover new treatment options for cancer patients,” said Durocher. “It’s rare that a new target is published alongside a launched clinical trial. This speaks volumes about the innovative capacity of the LTRI and its collaborators.”
Repare Therapeutics has initiated Phase I clinical trials in patients with CCNE1 amplified solid tumours, with initial results expected in late 2022.
The research was funded by Repare Therapeutics and the Canadian Institutes of Health Research.
A new approach for early cancer treatment known as radioligand therapy has been shown to reduce the risk of advanced neuroendocrine tumour progression and death by 72 per cent in otherwise challenging areas to treat.
The University of Toronto and the Centre for Addiction and Mental Health have received over $3 million to advance and commercialize radiopharmaceutical technologies for health care, and to train a new generation of scientists and clinicians.
A generous new donation from the Hold’em for Life Charity Challenge has established 12 new professorships for early-career clinician-scientists working in a broad range of cancer-related fields at U of T-affiliated hospitals across Toronto.