Target of new cancer treatment valid for breast as well as blood cancers: study

Results reinforce rationale for clinical trials expected to begin in May.

U of A oncology researcher John Mackey (left) and cell biologist Luc Berthiaume

U of A oncology researcher John Mackey (left) and cell biologist Luc Berthiaume are collaborators on new research showing that PCLX-001, an anti-cancer drug set to begin clinical trials this year, may work against breast cancer as well as lymphoma. (Photo: Faculty of Medicine & Dentistry; taken pre-COVID-19)

UPDATE Oct. 3, 2024: Pacylex Pharmaceuticals Inc. continues to make progress in developing its cancer treatment under the name zelenirstat, a once-per-day oral medication to treat blood and solid tumour cancers. Phase 1 first-in-human trials have been completed with minimal side-effects, and a safe and effective dose has been determined. Some patients responded positively to the drug as a treatment for their leukemia, lymphoma or colorectal cancers. Phase 2 trials will begin in Canada and the United States as funding is obtained. Pacylex was named 2024 Company of the Year by Bio Alberta for its strong performance and leadership within the field.

One more piece of the puzzle has fallen into place behind a new drug whose anti-cancer potential was developed at the University of Alberta and is set to begin human trials this year, thanks to newly published research.

“The results provide more justification and rationale for starting the clinical trial in May,” said first author John Mackey, professor and director of oncology clinical trials in the Faculty of Medicine & Dentistry. “It’s another exciting stepping stone to finding out if this is going to be a new cancer treatment.”

The drug PCLX-001 is designed to selectively kill cancer cells by targeting enzymes involved in myristoylation, a process key to the cell signalling system that is often defective in cancer cells. The molecule was originally developed by the University of Dundee as a treatment for African sleeping sickness. U of A cell biologist Luc Berthiaume was the first to realize it could work against cancer.

For this study, Mackey and his collaborators examined breast tumours from more than 700 women who had participated in a worldwide clinical trial for another drug in 1998. They found that 28 per cent of the tumours contained the enzyme N-myristoyltransferase 2 (NMT2), and that the patients who had those tumours were more likely to die during the following 10 years. 

“This will be the first time anyone has ever received PCLX-001 or a drug of this class. It’s very exciting, but there are many unknowns.“

John Mackey, U of A oncology researcher

“This shows that one of the targets of our drug, the enzyme NMT2, is clinically important to overall survival,” said Mackey, who is also co-founder and chief medical officer of Pacylex Pharmaceuticals, the U of A spinoff company set up to develop PCLX-001.

The researchers also reported that breast cancer cells treated with PCLX-001 in the laboratory were less viable, and that the drug slowed tumour growth by 90 per cent in mice with human breast cancer. These results are similar to those reported last fall on PCLX-001’s effect against lymphoma, a blood cancer which affects the infection-fighting cells of the immune system.

The clinical trial will take place in three Canadian centres, including the Cross Cancer Institute in Edmonton, and will enrol patients with advanced and previously treated lymphoma, breast, lung, colon or bladder cancers. The aim is to find the optimal dose of PCLX-001 for effectiveness and safety. 

“This will be the first time anyone has ever received PCLX-001 or a drug of this class,” Mackey noted. “It’s very exciting, but there are many unknowns.“

The study was funded by the Alberta Cancer Foundation and the Cure Cancer Foundation.

“We’ve had tremendous support from the local investor and donor communities for our made-in-Alberta innovation,” Mackey said.

In a free webinar on Jan. 27, hear from U of A medical oncologist John Mackey and cell biologist Luc Berthiaume about the new cancer drug PCLX-001, which is moving to human clinical trials this year and shows promise in treating blood cancers like non-Hodgkin lymphoma and leukemia as well as solid tumours.

Playing the Long Game to Conquer Cancer

In a free webinar on Jan. 27, hear from U of A medical oncologist John Mackey and cell biologist Luc Berthiaume about the new cancer drug PCLX-001, which is moving to human clinical trials this year and shows promise in treating blood cancers like non-Hodgkin lymphoma and leukemia as well as solid tumours.

Learn more and register

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