Success Story

Princess Margaret’s Dr. Tak Mak Refutes Critics, Sets Sights on Clinical Trials for ‘Sharpshooter’ Cancer Drug

In an exclusive interview with the CAHO Catalyst, Dr. Tak Mak, internationally acclaimed researcher at the Princess Margaret Cancer Centre, defends his team’s cancer-fighting ‘sharpshooter’ drug, on the eve of clinical trials, and refutes those who question the classification of this discovery as a breakthrough.

Under a white-hot media gaze, Dr. Tak Mak, Director of The Campbell Family Institute for Breast Cancer at the Princess Margaret Cancer Centre, together with the University of California’s Dr. Dennis Slamon, announced an extraordinary discovery on June 18, 2013: a new ‘sharpshooter’ drug that targets unstable cancer cells.

Forty-eight hours later, Globe and Mail public health reporter André Picard questioned the drug’s status as a genuine “breakthrough” and warned readers to take this news with a grain of salt because the drug had not yet been tested on humans.

The grain of salt, however, may be unnecessary. One month after the ‘sharpshooter’ announcement, two ringing endorsements present themselves: First, Health Canada gives its stamp of approval for the new drug. Similar consent is anticipated by the Food and Drug Administration (FDA).

Second, Mak’s research earns a slam dunk in the scientific community: an article in the Journal of Experimental Medicine―one of the most respected journals of its kind for more than a century, providing an important forum for advances in numerous research areas. Here, Mak and co-author Dr. Mona Gauthier reveal that they have solved a key piece in the cancer puzzle: how specific gene mutations (BRCA1) predispose women to breast and ovarian cancers.

Things are definitely falling into place as Mak’s team prepares for clinical trials where the ‘sharpshooter’ drug will be tested on humans. The term “breakthrough” becomes increasingly appropriate as each day passes.


Dr. Tak Mak, Director of Director of The Campbell Family Institute for Breast Cancer at the Princess Margaret Cancer Centre. Image provided by the University Health Network.

Mak Responds to Picard

In an exclusive telephone interview with the CAHO Catalyst from San Francisco―one of the 25 stops on Mak’s global speaking tour―he responds to Picard right away: “You have to understand, this drug was developed by a group of highly qualified professionals against a new class of targets. This is the breakthrough.

“It’s not something that somebody threw against the wall and said, ‘Hey it sticks.’ It’s based on a very well-formulated hypothesis. We synthesized thousands of very difficult compounds to make sure this is the perfect drug,” says Mak.

It is extremely rare for an academic group to have discovered and advanced a “first-in-class” drug candidate―that is, on the cutting edge of science―to this level. This is the first time since the late 1950s that an academic research hospital has independently developed an investigational new drug against a new class of anti-cancer targets.

“Academia doesn’t put something like this into a clinic and go this far, unless we know what we’re doing,” says Mak.

Dedicated to Scientific Enquiry

This research is of the highest caliber. When interviewing a scientist such as Mak―a veritable ‘rock star’ in the research world because he cloned a T-cell receptor gene in 1984, a discovery that’s regarded as the ‘Holy Grail’ of immunology―one cannot help but be struck by his dedication to scientific enquiry.

In fitting with this rigour, the road to discovery for his ‘sharpshooter’ drug could best be described as systematic and painstaking. It spanned a decade and engaged a team of 100 researchers from Canada, the United States and China.

Eager to share the spotlight, Mak extols his partners, Drs. Dennis Slamon and Homer Pearce. The latter, described by Mak as one of the world’s best medicinal chemists, introduced 24 new drugs into the clinic in 27 years, and actually came out of retirement from Lilly Research Laboratories to work on developing the ‘sharpshooter.’ Of Slamon, Mak says, “He has made more contributions to targeting [breast cancer] than anybody in the world.”

Drug Described as “A Gift from God”

The story of the drug’s discovery unfolds like a detective novel. Mak’s team zeroed in on one enzyme (PLK4) that plays a special role in cell division and discovered that its removal, in mice bred to develop human cancer, stopped the growth of cancer cells. Triple-negative breast cancer was an area of focus because it does not respond to Herceptin or hormonal therapy such as Tamoxifen.

Finding the right drug to ensure the enzyme’s removal was arduous. The team screened 10,000 different compounds, and synthesized thousands of new chemical entities to come up with the winning structure: CFI-400945, well poised to treat triple-negative breast cancer because the DNA sequences of this kind of cancer shows high levels of PLK4.

“We found a target that mainly hit the triple-negative breast cancer… And it turned out, in the end, that this was a gift from God,” Mak says. His team believes that this drug could also be effective on numerous other types of cancer, including ovarian, colorectal, lung, pancreatic and prostate cancers, as well as glioblastoma and melanoma.

This is a very different approach. Unlike chemotherapy, which attacks all fast-dividing cells including the cancerous ones, this new drug preferentially targets cancer cells―hence, the ‘sharpshooter’ tag that this new drug has rightfully acquired.
Known for his fondness of analogies, Mak draws the comparison of a horse and cart. “Rather than shooting the horses to try to stop the cart, we are targeting the cart: the genomically unstable cells,” he says.

Testing on Humans Starts

Armed with approval from Health Canada, Mak’s team next needs approval of the clinical trial from the Research Ethics Board at University Health Network (UHN). Then clinical trials can commence. The trials, which will take from six months to a year, will be led by Princess Margaret’s Dr. Philippe Bedard.

The initial phase of testing, designed to assess the safety of the drug, will likely involve 30 patients with breast or ovarian cancers that cannot be removed with surgery or treated with medication or radiation. “This phase will determine how strong a dose can be tolerated by patients,” says Mak. If the researchers find that the drug’s benefits outweigh its risks, then the next phase of testing would assess its effectiveness.

Mak’s team remains steadfast. “We are fervently devoted to making a difference to this very, very desperate group of cancer patients, breast and ovarian,” he says.

If it is effective, it could be less than a decade before the drug is approved for widespread use. Mak’s years of intrepid research may come to an end one day. “Will this drug work? I wish,” he says wistfully. “I gave it the best thought. If it works, I would be very happy… I would sign off and go play golf.”

To read the ‘sharpshooter’ press release, go to:; to read about how BRCA1 predisposes women to breast and ovarian cancers, see the press release from the Princess Margaret Cancer Centre, UHN:

The ‘sharpshooter’ research was made possible through support of Genome Canada, the Canadian Institutes of Health Research, The Campbell Family Institute for Breast Cancer at the Princess Margaret Cancer Centre and all those individuals who walked to raise funds.