Hope is on the horizon

Emmie Luther-Hiltz: "This kind of news means that maybe our children won’t have to live with such an overwhelming fear of developing cancer. Hope is on the horizon." (Danny Abriel Photo)

Hope has enormous significance for anyone who has experienced a cancer diagnosis.

Emmie Luther-Hiltz was just 33 years old when she woke up one Easter Sunday to find a golf-ball-sized lump in her breast – a lump that had not been there the day before.

“It was an aggressive cancer with a very tough prognosis,” says Ms. Luther-Hiltz, whose two children were just five and eight years old at the time. After having her breast and grossly malignant lymph nodes removed, she endured six months of chemotherapy.

Remarkably, she is alive and well 16 years later, but that doesn’t mean her fear of cancer has gone away. “Breast cancer can recur after 15, even 20 years,” she says. “I’ve had a number of scares and, just last year, had my other breast removed when we found a benign lump.”

As a cancer survivor who works closely with patients through Cancer Care Nova Scotia, Ms. Luther-Hiltz is heartened by the recent news that Dalhousie virologist Patrick Lee has found a way to kill the very cells that lead to cancer recurrence. These are the cancer stem cells. Like a queen ant churning out eggs, cancer stem cells continuously produce new cancer cells.

“You can kill all the ants in the anthill, but if you don’t get the queen, you will still have ants,” says Dr. Lee, Cameron Chair in Basic Cancer Research at the Dalhousie Medical School. “Unfortunately, chemotherapy and radiation do not eliminate the cancer stem cells and they keep on producing cancer cells.”

Dr. Lee’s landmark finding – that a common virus effectively targets and kills breast cancer stem cells – recently appeared in the prestigious journal, Molecular Therapy. When the story broke, it led local newscasts, spread like wildfire online, and sparked a buzz of excitement in the cancer community.

“This is a fabulous discovery,” says Emmie Luther-Hiltz. “What it means is hope. Hope has
enormous significance for anyone who has experienced a cancer diagnosis.”

Dr. Lee is thrilled by his team’s findings, as he has been on a mission for the past two years to prove that human reovirus can kill cancer stem cells. Unlike most cancer experiments, which rely on cancer cell lines developed for the laboratory, Dr. Lee’s experiments used fresh tumour tissue from local breast cancer patients.

“Cell lines are grown in vitro so long, it’s hard to be certain your experiment is reflecting real life,” says Dr. Lee. “It’s very exciting to see these results in real biopsy material.”

He credits his collaborator, Dr. Carman Giacomantonio, a Capital Health surgeon and associate professor in Dalhousie’s Division of Surgical Oncology, for his dedication to the project. “Carman would bring us the breast tumour tissues within an hour or two of removing them from a patient.”

Whenever tumour tissues arrived in the lab, postdoctoral fellow Paola Marcato and research assistant Cheryl Dean worked late into the night, implanting tiny pieces of tumour in the mammary fat pads of mice while the grafts were still fresh enough to take hold and form tumours.

After injecting reovirus into the tumours, the researchers noted how quickly the cancer stem cells were dying compared to the regular cancer cells. “The cancer stem cells died at the same rate as the regular cancer cells,” says Dr. Lee. “This is exactly what we had hoped to see.”

Dalhousie virologist Patrick Lee: "It’s very exciting to see these results in real biopsy material." (Danny Abriel Photo)

The media spotlight is nothing new for Dr. Lee. In 1998, he galvanized the world scientific community with his first groundbreaking discovery – that reovirus selectively targets and kills cancer cells without harming healthy cells.

“But proving we can target cancer stem cells is even more exciting than the original discovery,” he says. “It means we finally have a way to get to the root of the problem.”

Reovirus kills cancers of the lung, prostate, colon, ovary and brain, as well as lymphoma and melanoma, as shown by Dr. Lee’s previous studies. “We have every reason to believe that reovirus will kill the cancer stem cells in these and other kinds of cancer,” he says. “We plan to test it against prostate cancer stem cells next.”

As the researchers explore additional potential in their lab, a Calgary-based company, Oncolytics Biotech, is testing the virus in cancer patients.

“We have had dramatic results in both phase one and phase two clinical trials in a wide range of cancers, including sarcomas, ovarian, pancreatic and advanced head and neck cancers,” says Matt Coffey, the company’s chief operating officer. “Now we’re getting ready to launch international phase three clinical trials.”

The pair began working together at the University of Calgary on the original reovirus discovery. Oncolytics Biotech was launched to develop and test reovirus-based cancer therapies.

“Getting the cancer stem cells is key,” says Dr. Coffey. “We’re not here to delay cancer, we’re here to cure it.”

The worst side effects in cancer patients have been mild, flu-like symptoms, he notes. “The virus causes no disease, which makes it safe for patients and easy to work with.”

Meanwhile, Dr. Lee and his team are learning more about the cancer-killing advantages of reovirus every day.

“We think of cancer cells being so tough, but they are weak in the face of the virus,” says Dr. Lee. “Cancer cells are not capable of mounting a defense against the reovirus. They actually help the virus reproduce and form new virus particles that are many times more infectious than the parent virus!”

These virulent particles then rupture the cancer cell and circulate around the body, killing not just the primary tumour, but also cancer cells that have spread. At the same time, they stimulate a powerful anti-cancer immune response.

Dr. Lee and postdoctoral fellow Shashi Gujar are working on a way to maximize this anti-cancer response, while minimizing the immune system’s reaction to the reovirus. “We want to tone down the anti-virus response so reovirus can freely infect and kill cancer cells while helping the body mount its own anti-cancer attack,” notes Dr. Lee.

Drs. Marcato and Gujar are among the many young cancer researchers who have flocked to Dalhousie since Dr. Lee joined the medical school in 2003. Senior researchers have also come to work in the university’s increasingly dynamic cancer research community, which has grown from a handful of scientists to more than 50 principal investigators.

This growth spurt began with a remarkable gift to the Dalhousie Medical Research Foundation. In 1999, the late Beatrice Hunter bequeathed $12.5 million to the foundation for cancer research, in memory of her parents, Dr. Owen and Mrs. Pearle Cameron. This gift provides $500,000 to cancer research at Dalhousie Medical School each year. It also created the Cameron Chair in Basic Cancer Research, the leadership position that attracted Dr. Lee to Dalhousie.

Dr. Lee is a founding member of the Beatrice Hunter Cancer Research Institute, established in April 2009 to foster a coordinated cancer research effort in Atlantic Canada.

“Patrick Lee has helped create an environment where world-class cancer research can thrive,” says Theresa Marie Underhill, chief operating officer of Cancer Care Nova Scotia, which co-funds his cancer stem cell research with the Canadian Breast Cancer Foundation–Atlantic Region. “It’s rare for us, as the provincial cancer agency, to fund basic research, but Dr. Lee’s reovirus work is very close to patients, and even involved cancer patients going through surgery, so it was the right fit.”

“For an organization dedicated to a future without breast cancer, research is the most significant part of our work,” says Nancy Margeson, CEO, Canadian Breast Cancer Foundation–Atlantic Region. “To have a breakthrough of this magnitude substantiates our faith that one day our vision will come true.”

The Canadian Institutes of Health Research, the Canadian Cancer Society and the Terry Fox Foundation are also staunch supporters of Dr. Lee’s research. As he notes, every grant and every discovery builds on the one before, leading to those eureka moments that change everything.

For Emmie Luther-Hiltz, whose parents, grandparents, aunts, uncles and siblings have all battled cancer, Patrick Lee’s discoveries offer hope for the future. “Cancer is a way of life in our family,” she says. “This kind of news means that maybe our children won’t have to live with such an overwhelming fear of developing cancer. Hope is on the horizon.”