The underlying tenet of Personalized Cancer Medicine is that no two cancers are the same. Each patient has a unique genetic code, producing tumours of various sizes, locations, metastases, and drug responses.

Given this tremendous variation, our clinicians and researchers at The Princess Margaret are developing ways to understand each individual’s cancer at its origins. They are performing basic science research to unravel the biochemical, molecular and cellular signaling pathways underlying the process of tumour development. Not only will this help us to understand the causation for these inter-patient discrepancies, but it will also lead us to discover new drugs that will be targeted and optimized for each patient’s specific condition.
The fundamental purpose of cancer research is to discover sources of weakness in tumours. If we can identify specific tumour vulnerabilities, we will be able to target cancer through more effective and specialized drugs that can exploit these processes.

At The Princess Margaret, we are fortunate to house the BRAS Drug Development Program – an internationally renowned drug testing facility that is committed to the translation of scientific findings (i.e. new biological targets) into novel anti-cancer drugs.

The program encompasses all phases of early stage drug development, and it is paving the way in ensuring that patients have rapid access to the newest and most promising cancer drugs. The drug development process, however, is no easy pursuit. It requires the collective efforts of world-class chemists, biologists and physicists, as well as major investments in molecular diagnostics and tumour profiling technology, and rigorous testing procedures to ensure patient safety as the drug is introduced to clinic.

The BRAS Drug Development Program works closely with the Cancer Clinical Research Unit (CCRU) – The Princess Margaret’s conduit for clinical research. 

Clinical trials are research studies that involve people. In order for a drug to become clinically available, it must pass through three to four phases of clinical trials (outlined at right) to ensure that it is safe, tolerable, and effective.

The BRAS Drug Development Program is primarily focused on Phase I and II clinical testing – where new drugs are being tested for the first time on humans. Dr. Lillian Siu, who is Co-Director of the BRAS Drug Development Program, is also the Director of the Phase I Clinical Trials Program at The Princess Margaret. This program has the greatest number of Phase I patients treated annually in any clinical trials program, and the largest number of active Phase I trials (on average 25-30) at any one time, in Canada. It is the only Phase I program in Canada to receive a grant from the U.S. National Cancer Institute (NCI).

Dr. Amit Oza, the other Co-Director of the BRAS Drug Development Program, has been the principal investigator and co-investigator in Phase I, II, and III trials for gynecological cancer and advanced colorectal malignancies.


A)  Dr. Tak Mak’s “First-In-Class” Cancer Sharpshooting Drug
It was only a matter of time before our very own Dr. Tak Mak, most famous for his groundbreaking discovery of the T-cell Receptor, made another major contribution that may revolutionize cancer therapy across the globe. 

After years of collaboration with Dr. Dennis Slamon of the University of California, the dynamic duo discovered and advanced a novel “first-in-class” cancer sharpshooting drug. The drug targets the enzyme PLK4, which was observed by Drs. Mak and Slamon to play a crucial role in cancer cell division. The new drug, CFI-400945, will enter clinical trials in the months ahead. We are extremely excited to see its effects on cancer patients, and are optimistic based on its ability in laboratory to inhibit growth of human breast and ovarian cancers, as well as colorectal, glioblastoma, lung, melanoma, pancreatic, and prostate cancers.

B) Investigating Genes that Drive Cancers 
Understanding the genetic makeup of a cancer underlies the concept of precision medicine, where therapies are tailored to the cancer characteristics. One gene that drives many of the advanced cancers of the brain, prostate, breast, and other tissues is named PTEN. Working on decyphering the biology of PTEN, Dr. Vuk Stambolic and his team have discovered a particular vulnerability of tumours featuring PTEN loss. They are currently working with clinicians at The Princess Margaret to introduce these concepts into the clinic, with the intent of developing therapies for these otherwise difficult to treat cancers. 

Similar to these efforts, Dr. Mitsuhiko Ikura is leading a project on the characterization of another key cancer gene, Ras, and its protein product, directly feeding attempts to counter Ras activity in many human cancers. These projects represent only some of the basic research programs within The Princess Margaret looking to bridge their discoveries to the clinic.  

Research into the development of new anti-cancer drugs is an exciting and fast-paced environment. Our goal is to ultimately get research out of the lab and into clinical trials, and doctor’s offices, to provide our patients with the latest and most promising anti-cancer drugs.  

Dr. Mak’s breakthrough drug is a perfect example of how philanthropy drives innovation – his drug was developed using funding from our generous donors. With your support, we will continue to discover ways to capitalize on tumour biology through targeted therapies and new drug development.