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.

The funding is made possible by the gift of $30 million made in 2016 by philanthropists Ernest and Evelyn Rady in support of health sciences at the university. The fund will allocate a total of $1 million over three years to support collaborative research by faculty members.

The one-year grants are designed to seed short-term projects that combine the expertise of researchers from various departments and colleges of the Rady Faculty of Health Sciences.

“All four of these interdisciplinary teams have proposed cutting-edge science,” said Dr. Peter Nickerson, vice-dean research of the Rady Faculty. “These are exciting projects that cover the spectrum from basic to clinical research, each with the potential for high impact in the short term.”

Here are the projects chosen for funding in 2019:

Analyzing medications in human milk

Dr. Lauren Kelly

Dr. Lauren Kelly, assistant professor of pediatrics/child health in the Max Rady College of Medicine and scientist with the Children’s Hospital Research Institute of Manitoba (CHRIM), will lead a study of breast milk. Mothers who take medications, and their health-care providers, are often concerned about infants’ exposure to drugs in breast milk. This can deter breastfeeding or deny moms safe use of medicines.

Kelly’s team includes researchers from the College of Nursing, College of Pharmacy, Manitoba Centre for Health Policy and CHRIM. After reviewing what medicines breastfeeding women in Manitoba use, they will conduct a pilot project to collect and analyze breast milk. The evidence obtained will advance the understanding of medication safety during breastfeeding.

A further goal is to develop methods for storing anonymized medication data with milk samples, allowing for follow-up research.

Applying artificial intelligence to health research

Dr. William Leslie

A team led by Dr. William Leslie, professor of internal medicine and radiology in the Max Rady College of Medicine, has already had success at harnessing artificial intelligence. The team has “taught” a machine to find vertebral fractures on bone-density scans. This helps to identify patients at high risk for another fracture.  

The new study will continue this machine-learning research, enhance the infrastructure for it, and promote machine-learning collaborations within and beyond the Rady Faculty of Health Sciences.

Leslie’s team, which includes researchers from the department of radiology and the College of Pharmacy, will share lessons they have derived from “teaching” machines, in terms of requirements such as image processing and computer programming. A key goal is to help other researchers enter this fast-paced field.

Understanding a non-invasive thyroid tumour

Dr. Sabine Mai

Dr. Sabine Mai, professor of physiology, biochemistry/medical genetics and human anatomy/cell science in the Max Rady College of Medicine, Canada Research Chair in genomic instability and nuclear architecture in cancer, and senior investigator at the Research Institute in Oncology and Hematology, leads a team that will investigate a type of thyroid tumour called a “non-invasive follicular thyroid neoplasm with papillary-like nuclear features” (NIFTP).

Because this tumour is non-invasive, it may be over-treated if it is diagnosed as aggressive cancer. This study will compare NIFTP to other sub-types of thyroid cancer in order to predict its behaviour and tailor its clinical management.

With team members from pathology/immunology and surgery, the study will examine NIFTP at the genetic level. It will look, for example, at the 3D organization of telomeres (the ends of chromosomes). The project aims to refine the diagnostic criteria for NIFTP.

Investigating the genetics of HIV risk

Dr. Lyle McKinnon

A study led by Dr. Lyle McKinnon, assistant professor of medical microbiology and community health sciences in the Max Rady College of Medicine, will build on the previous finding that vaginal inflammation in women increases HIV susceptibility. The underlying reasons why some women have this inflammation are unclear.

The team recently analyzed the genetic profiles of more than 200 young women in South Africa. They found several gene variants that are associated with genital inflammation and/or HIV acquisition.

With team members from medical microbiology/infectious diseases, immunology and community health sciences, this study seeks to validate this finding in a larger sample of South African and Kenyan women, and to investigate more precisely how genes influence inflammation and HIV susceptibility. The ultimate goal is to develop new HIV prevention strategies.

VIEW FULL PROJECT DESCRIPTIONS.

The 2018 Rady Innovation Fund recipients, Dr. Thomas Klonisch, Dr. James Nagy and Dr. Kathryn Sibley, will present their findings on December 17, click for event info.