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Finding new targets for treatment within the tumour microenvironment to personalize cancer therapies

A leading team of scientists at Toronto’s Princess Margaret Cancer Centre is set to expand its groundbreaking research into the effects of low oxygen levels (hypoxia) on tumour aggressiveness thanks to renewal funding from the Terry Fox Research Institute.

Led by Drs. Marianne Koritzinsky and Michael Milosevic, the group will receive $6M over the next six years after being awarded a Terry Fox New Frontiers Program Project Grant (PPG). This grant will allow the team to continue studying how hypoxia interacts with other elements within the tumour microenvironment to make cancers spread and become resistant to treatment.

“During previous iterations of the project we learned that the tumour microenvironment is a unique ecosystem made up of different cells, and that its composition (including hypoxia) can drive the aggressiveness of a cancer and determine if a patient’s tumor is resistant to therapy,” explained Dr. Koritzinsky, a hypoxia specialist at Princess Margaret and a former Terry Fox New Investigator. “With this new funding we hope to continue gaining a deeper biological understanding of the role each element in the microenvironment plays so we can begin targeting specific vulnerabilities in each patient to improve their outcomes.”

The new PPG is officially called Triggers and Targets in the Tumour Microenvironment and consists of four project groups that will look at four aggressive types of cancer: pancreatic cancer, glioblastoma multiforme, castrate-resistant prostate cancer and cervical cancer. While each project is slightly different, their main goal is the same: to find vulnerabilities within the tumour microenvironment of each patient that can be exploited to personalize therapies.

All four projects integrate basic laboratory, translational and clinical components, which accelerates discoveries that benefit patients. Two project groups will set up clinical trials over the next couple of years. These trials will test combination therapies that target the tumor microenvironment in castrate-resistant prostate cancer and cervical cancer to bring new hope to patients with these hard-to-treat diseases.

The castrate-resistant prostate cancer trial, which will be performed by a team co-led by Dr. Housheng Hansen He, a current recipient of the Terry Fox New Investigator Award, will seek to improve the efficacy of blocking androgen receptors by simultaneously targeting hypoxia. Meanwhile, the clinical trial focusing on cervical cancer will look at a way to improve response to radiation treatment by blocking a pathway that causes immune cells to flood a tumour site, driving treatment resistance.

“We are on the cusp of having some major influences on how we treat patients with cancer, which is really exciting,” says Dr. Milosevic, who is the director of research for radiation medicine at Princess Margaret and who will be co-leading the cervical cancer group.

  • To read about this project in French, please click here.


Building from past successes

This will be the third time that the Tumour Hypoxia Group at the Princess Margaret Cancer Centre is funded by TFRI. In previous iterations of the project, the team has made some impressive breakthroughs, including:

By building on these discoveries and moving the research further down the pipeline, the team hopes to begin implementing their new discoveries as soon as possible, to help patients and continue learning more from them.

“By capitalizing on the flow of information back and forth from the clinic to the lab we will advance the science on how the microenvironment influences cancer progression, cancer control, metastasis formation and treatment response in our patient population,” says Dr. Milosevic. “I think it's hugely exciting because over the next few years we can make a really big difference into how patients with cancer are treated.”

Previously funded projects