After testing 8,500 drugs, the research team discovered that poziotinib – a drug that already exists and is approved for other cancers – reduced breast cancer brain metastasis tumours in mice after two weeks of treatment.

Brain metastasis occurs when cancer cells spread from one part of the body to the brain and form tumours. This study focused on HER2-positive breast cancer, which contains abundant levels of HER2 protein that promotes the growth of cancer cells.

[Left to right] Dr. Danyyl Ippolitov, Dr. Sabine Hombach-Klonisch and Dr. Thomas Klonisch.

Brain metastasis can happen years after successfully treating a breast cancer tumour and occurs in about 50 per cent of individuals with HER2-positive breast cancer, says Dr. Sabine Hombach-Klonisch, professor and head of the department of human anatomy and cell science at the Max Rady College of Medicine, Rady Faculty of Health Sciences.

“This is a huge success,” says Hombach-Klonisch, a lead author of the study that was recently published in the journal Cancer Research.

“We set out to look for drugs that would penetrate the brain, and also effectively reduce the metastatic brain tumour and we found a drug that did that. It’s a leap forward in reducing the tumour mass in the brain.”

The scientists were faced with finding a drug that could penetrate the blood-brain barrier, a layer of cells that acts as a filter and protects the brain. Hombach-Klonisch says that many cancer drugs that work in other parts of the body can’t enter the brain in high enough concentrations to be effective, and brain cells surrounding the tumour produce growth factors that can cancel the success of many drugs.

“The brain penetrability of current drugs is low,” Hombach-Klonisch says. “We have shown that poziotinib actually has a high concentration in the brain after administration. Drug levels remain long enough to have a therapeutic concentration before they drop.”

Study co-authors from the Max Rady College of Medicine include first author Dr. Danyyl Ippolitov, research associate in the department of human anatomy and cell science, Dr. Jason Beiko, assistant professor of surgery, Dr. Marc Del Bigio, professor of pathology, and Dr. Thomas Klonisch, professor of human anatomy and cell science.

“This research is important because many patients with breast cancer are waiting with uncertainty, not knowing if brain metastases will occur and whether there will be a drug that’s effective in treating it, so I think it gives them hope,” Hombach-Klonisch says. 

Hombach-Klonisch anticipates the drug and its use in treating brain tumours will soon be tested in clinical trials.

She says the research project will continue because they have plenty of questions to answer, such as how many tumour cells are left after treatment with poziotinib and what needs to be done to prevent recurrent tumour growth?

The study was funded by the Cancer Research Society in partnership with the Canadian Institutes of Health Research (CIHR) and CancerCare Manitoba. Studentship funding was received from CIHR.

After 15 years of steadily building up its research and teaching branches, the department currently has 16 core faculty members.

“The demands on research and teaching of our faculty members change constantly and it is a daily challenge to remain competitive,” says Hombach-Klonisch. “My vision is to promote innovation in research, foster collaborations and provide excellence and novelty in teaching to the community we serve.”

Hombach-Klonisch, who stepped in to her new position at the beginning of January, is the first woman to head the department. She joined the University of Manitoba in 2004, teaching anatomy and running her research program on late stage brain and breast cancer.

The department has research strength in four areas: cancer, neurosciences, cardiovascular and applied musculoskeletal research. Researchers study cell-to-cell communication and how structure-function relations on the cellular and molecular level affect tissue development, function and regeneration. Their nationally-funded research programs were recently strengthened by the recruitment of a Tier 2 Canada Research Chair in Cell Stress and Inflammation.  

“We are continuing to build on our strong nationally-funded interdisciplinary biomedical science programs and further expanding collaborative research teams,” says Hombach-Klonisch.

Dr. Hombach-Klonisch in the histology lab’s imaging facility.

Going forward, she is hoping to increase effective networking among scientists within the department and beyond.

“Our department is unique because we frequently teach together with cross-appointed clinical colleagues,” says Hombach-Klonisch. “This helps to network with clinical colleagues in surgery, internal medicine, radiology, pathology and oral biology and build bridges between teaching and research activities.”

On the education front, Hombach-Klonisch says the future of anatomy teaching includes tailored teaching strategies for the programs in the different colleges at the Rady Faculty of Health Sciences, including medicine, dentistry, nursing, rehabilitation sciences and pharmacy.

“Our faculty teaches a diverse student body in the health professions from undergraduate to the graduate and postgraduate level,” she says.

Hombach-Klonisch sees an opportunity for the department to introduce anatomy and histology to undergraduate education in the Rady Faculty’s new Bachelor of Health Sciences program, to prepare these students to enter a graduate or health professional program.

Since 2010, Hombach-Klonisch has served as the section head for gross anatomy with responsibilities for the cadaver-based teaching programs in the department, a strength of the department for many years. The recent renovations and opening of the $4.3-million Dr. George Yee Laboratory of Anatomical Sciences provides a cutting-edge laboratory that is an inviting and creative space for trainees at the beginner and advanced levels of anatomy learning.

“The Dr. George Yee Laboratory of Anatomical Sciences offers the best possible education for our health professionals with its clinical learning space and state-of-the-art equipment. It encourages productive, innovative and interactive collaborations in health education,” she says, adding the department is poised to build on its strengths of vibrant teaching methods and internationally-recognized published researchers in their respective fields.

“I am excited about the opportunity to work with the dedicated and highly motivated team of faculty, trainees and staff at the anatomy department.”