Targeting ROGUE ENZYMES in Rare Breast Cancer
When Scientist Mark Bray talks about breast cancer, he sounds like someone discussing a worthy opponent. One which he very much wants to defeat.
“As cancer is evolving and transforming in the body, the checks and balances that protect us break down. So, what we are really after is an ‘Achilles heel,'” says Dr. Bray.
Since 2012, Dr. Bray has directed the efforts of the multi-disciplinary drug discovery and development team at The Campbell Family Institute for Breast Cancer Research at The Princess Margaret.
Dr. Bray works alongside The Campbell Family Institute Director Dr. Tak Mak, who is known for advancing the field of immuno-oncology with the cloning of the T-cell receptor, considered the holy grail of the immune system.
For the past few years, Dr. Bray, Dr. Mak and the drug discovery team have focused on two enzymes, PLK4 and TTK, which have been shown to promote cancer progression.
They are developing new drugs to treat breast cancer, particularly the difficult to treat triple negative breast cancer.
“Despite 30 years of relentless drug discovery around these types of proteins, no drug has ever been developed to target these particular enzymes,” says Dr. Bray.
“If we could develop drugs that would block these enzymes … they could be used to target subsets of untreatable breast cancer and potentially other types of cancers.”
The team developed an inhibitor to the PLK4 enzyme, which is about to enter Phase 2 clinical trials in both breast and prostate cancers across the country. They have also opened a trial in leukemia.
A TTK inhibitor has also been developed, which has been in a Phase 1 clinical trial since late 2016. A new clinical trial in breast cancer, combining the TTK drug with the chemotherapy drug Taxol in breast cancer, will open across Canada this fall.
Dr. Philippe Bedard, Oncologist at The Princess Margaret, has been the lead Clinical Investigator for the Phase 1 trials of both of The Campbell Family Institute drugs and will be involved with the upcoming Phase 2 programs.
“We're still in the process of figuring out the right dose and schedule for both compounds, but we've been very pleased with the progress we've made so far,” says Dr. Bedard. “The drugs are extremely well tolerated, patients feel good on them and we think there's a strong scientific basis that eventually using them in combination with chemotherapy will offer greater benefits.”
Both inhibitors have shown promise, but Dr. Bray knows not to get his hopes up too early in the drug development process.
“We would obviously like our drugs to be the universal cure for cancer of all time,” he says. “And we know they won't be. But maybe, just maybe, we will have provided something that helps. And that's really the thing that drives us: the hope of seeing the benefit to the patients.”