Study maps decade of discovery to potential anticancer agent (w/ Video)

July 17, 2014, University Health Network

The journal Cancer Cell today published research led by Dr. Tak Mak mapping the path of discovery to developing a potential anticancer agent.

"What began with the question 'what makes a particular aggressive form of keep growing?' turned into 10 years of systematic research to identify the enzyme PLK4 as a promising therapeutic target and develop a small molecule inhibitor to block it," says Dr. Mak, Director of The Campbell Family Institute for Breast Cancer Research at the Princess Margaret Cancer Centre, University Health Network. He is also Professor, University of Toronto, in the Departments of Medical Biophysics and Immunology.

In the lab, the scientific team used an approach that combined functional RNAi analysis with gene expression analysis in breast cancer-derived cell lines and in human breast cancers replicated in mice. Using these multidimensional datasets for human breast cancer, PLK4 was identified as a candidate target among 10,000 other targets for the development of anticancer therapeutics.

"The research showed that the aggressive form of basal breast cancer cells may be dependent on PLK4 for survival and that depleting it induced cell death," says Dr. Mak. "This finding led to the identification of CFI-400945, a selective and orally active inhibitor of PLK4, which was shown to have significant antitumor activity as a single agent in a variety of preclinical tumor models."

Another key finding was observing the inhibitor effect on tumor models with a gene PTEN deficiency as a biomarker – of huge interest because PTEN, a tumor suppressor, is known to be defective in as many as half of all advanced solid tumor cancers.

"If clinical testing supports our hypothesis that PTEN is a predictive biomarker for CFI-40095, we will have another way to tailor personalized cancer medicine based on an individual's genetics," says Dr. Mak.

Although was the initial focus and featured in the study published online today, the team has also conducted experiments with other types of solid tumors, with similar results. The next phase of research will involve testing in humans, which was approved last year by Health Canada and the U.S. Food and Drug Administration.

"It may take several more years to determine the benefit for patients," says Dr. Mak, "but we are happy to be able to provide this opportunity for our patients. We remain optimistic that we may have found a novel way to treat cancer." Dr. Mak is an internationally acclaimed immunologist renowned for his 1984 cloning of the genes encoding the human T-cell receptor.

Explore further: Cancer researchers discover how BRCA1 mutation starts breast, ovarian cancers

Related Stories

Cancer researchers discover how BRCA1 mutation starts breast, ovarian cancers

July 15, 2013
Scientists led by Drs. Mona Gauthier and Tak Mak at The Campbell Family Institute for Breast Cancer Research at the Princess Margaret Cancer Centre have solved a key piece in the puzzle of how BRCA1 gene mutations specifically ...

Research team identifies mechanism of chemotherapy resistance in inflammatory breast cancer

July 8, 2014
Researchers at Roswell Park Cancer Institute (RPCI) have identified a mechanism of breast cancer cells that leads to chemotherapy resistance in inflammatory breast cancer. These preclinical findings, published online ahead ...

Cancer scientists discover new way breast cancer cells adapt to environmental stress

May 15, 2011
An international research team led by Dr. Tak Mak, Director, The Campbell Family Institute for Breast Cancer Research at Princess Margaret Hospital (PMH), has discovered a new aspect of "metabolic transformation", the process ...

Scientists link 'oncometabolite' to onset of acute myeloid leukemia

July 4, 2012
A team of international scientists led by principal investigator Dr. Tak Mak at the Princess Margaret Cancer Centre, University Health Network, has identified a causative link between the product of a mutated metabolic enzyme ...

Cancer researchers PTEN discovery provides knowledge to individualize treatment

July 25, 2013
Scientists at the Princess Margaret Cancer Centre have discovered a function of the tumor suppressor gene PTEN that helps explain why certain promising therapies fail in many cancer patients, a finding that could aid in delivering ...

Recommended for you

Boosting cancer therapy with cross-dressed immune cells

January 22, 2018
Researchers at EPFL have created artificial molecules that can help the immune system to recognize and attack cancer tumors. The study is published in Nature Methods.

Workouts may boost life span after breast cancer

January 22, 2018
(HealthDay)—Longer survival after breast cancer may be as simple as staying fit, new research shows.

Cancer patients who tell their life story find more peace, less depression

January 22, 2018
Fifteen years ago, University of Wisconsin–Madison researcher Meg Wise began interviewing cancer patients nearing the end of life about how they were living with their diagnosis. She was surprised to find that many asked ...

Single blood test screens for eight cancer types

January 18, 2018
Johns Hopkins Kimmel Cancer Center researchers developed a single blood test that screens for eight common cancer types and helps identify the location of the cancer.

Researchers find a way to 'starve' cancer

January 18, 2018
Researchers at Vanderbilt University Medical Center (VUMC) have demonstrated for the first time that it is possible to starve a tumor and stop its growth with a newly discovered small compound that blocks uptake of the vital ...

How cancer metastasis happens: Researchers reveal a key mechanism

January 18, 2018
Cancer metastasis, the migration of cells from a primary tumor to form distant tumors in the body, can be triggered by a chronic leakage of DNA within tumor cells, according to a team led by Weill Cornell Medicine and Memorial ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.