Scientists at Sinai Health say a new drug designed to block an enzyme essential for the survival of certain cancer cells shows promise in curbing tumour growth.
The preclinical findings, published this month in Nature, describe a new drug designed from the use of CRISPR-Cas9 gene editing technology at Sinai Health’s Lunenfeld-Tanenbaum Research Institute (LTRI).
A team of researchers, led by senior investigator Dr. Daniel Durocher, identified genes that are essential for the viability of CCNE1-amplified cancer cells, which are characteristics of certain 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 RP-6306, a drug that blocks PKMYT1 activity and effectively kills the cancer cell.
“These cancer cells depend on the PKMYT1 enzyme to survive,” said Dr. Durocher. “Our preclinical data shows enormous promise in the drug RP-6306’s ability to target these types of tumors and profoundly inhibit tumor growth.”
Currently, tumors with CCNE1-amplification have very few therapeutic options. Dr. David Gallo, 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 tumors with amplifications of CCNE1 are notoriously resistant to current standard-of-care treatments,” said Dr. Gallo, co-first author of the 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. In 2016, Durocher founded Repare Therapeutics, alongside another LTRI scientist Dr. Frank Sicheri. Their company is built upon the concept of synthetic lethality, a process that uses 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 Dr. 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 tumors. Initial results are expected in late 2022.
Work on CCNE1 in the Durocher laboratory was led by Dr. Gallo and was funded by Repare Therapeutics and the Canadian Institutes of Health Research (CIHR).