From left to right: Eric Price, Andrew Freywald, and Franco Vizeacoumar. (Photo credit: Daniel Hallen)

U of S researchers target the most aggressive of breast cancers

More than 25,000 women in Canada are diagnosed every year with breast cancer, with no specific therapy available to target the most aggressive sub-type called triple-negative breast cancer (TNBC).

By Sarath Peiris

“Unfortunately, a lot of patients with triple negative breast cancer die relatively fast,” said University of Saskatchewan cancer researcher Andrew Freywald, who has been awarded $558,452 by the Canadian Institutes for Health Research to find methods to target TNBC directly and improve patient survival.

Freywald, who has established an experimental system that uses mouse models to ascertain the initiation and growth of cancerous tumours, is collaborating on the research with Franco Vizeacoumar, clinical assistant professor in the U of S College of Medicine and research scientist at the Saskatchewan Cancer Agency, and Eric Price, assistant professor in chemistry and Canada Research Chair in Radiochemistry.

The aim is to develop new, personalized therapies to target and eliminate triple negative breast cancer. About 10 trainees including post-doctoral fellows, graduate students and summer students will be involved in their four-year project.

The researchers have initially focused on a cell-surface receptor (CSR) molecule, which promotes aggressive tumour development. It has been found to be overexpressed (produced in large quantities) in many cancer tumours including TNBC.

Freywald worked with Massachusetts-based Biomirex Inc., which makes synthetic antibodies for therapeutic and diagnostic purposes and also developed a synthetic antibody that targets the receptor molecules.

“Even though the antibody we developed is highly efficient and looks promising for breast cancer therapy, it still leaves about 20 per cent of the tumour resistant to the treatment,” said Freywald.

So while the antibody drug would prolong a patient’s survival, there is a high chance the tumour will regrow and spread. An additional problem is that not all triple negative breast cancer patients would have a high expression of receptor molecules on the surface of their tumour to be targeted by the antibody.

The challenge is twofold, Freywald said.

“We need to identify patients with the accessible CRS molecules because they are the patients who will benefit. And we need a method to deal with the resistant cells in the tumour.”

As the genome specialist, Vizeacoumar is using sophisticated screening tools to identify new target genes that are essential for the survival of the resistant cancer cells. By developing and applying additional antibodies that inactivate these target molecules, the resistant cancer cells also can be eliminated.

The effectiveness of the antibodies will be tested in mouse models developed with human triple negative breast cancer tumours.

As the nuclear imaging specialist, Price is developing novel methods that will identify patients whose cancers are of the correct type and whose tumours are accessible to therapy that includes the anti-cell surface receptor drug.

With support of the specialized laboratories of the Saskatchewan Centre for Cyclotron Sciences, operated by the Fedoruk Centre at the U of S, Price has produced a new type of chelator — a molecule that binds strongly to a radioactive metal and attaches it to an antibody, which can then be injected into a patient to seek out and “light up” diseased tissue.

Price’s new chelator is far superior to the chelator used currently for Positron Emission Tomography (PET) imaging in local hospitals.

“In the PET image, you are precisely tracking the radioactivity,” Price said. “You get good data from it and you can see the whole patient. It effectively makes the person transparent.”

The PET imaging process, which is non-invasive, yields a 3-D image of the exact locations and sizes of cancer tumours, where the antibodies and their radioactive passengers stick. The brightness of the tumour images will quantify the presence of targets for subsequent antibody-based therapies.

“This is the whole idea of personalized medicine,” said Price.

Vizeacoumar said there’s no magic bullet for cancer, and combination therapy is becoming the systematic approach. Genome-wide screening to identify complementing targets and using nuclear imaging to personalize treatment is the way forward with treating this aggressive form of cancer.

“Overall, this is a powerful project that should bring us to a very effective, targeted therapeutic approach for treating this cancer,” said Freywald.

Sarath Peiris is Assistant Director Research Profile and Impact at the U of S.