Ganging up on cancer
A Vancouver specialist spearheads a team approach
When Dr. David Huntsman discovered a mutated gene common in ovarian cancer, two years ago, he did what very few scientists do. He emailed the competition.
Huntsman is not just a brilliant genetic pathologist working in the rabbit warren offices of the B. C. Cancer Agency — he is also co-chairman of a unique interdisciplinary team that has united clinicians, statisticians, pathologists and other researchers from two Vancouver hospitals and the B. C. Cancer Agency.
In this time of patented genes and career-building discove r i e s , w h e n m o s t researchers work in isolation zealously protecting their work, Huntsman’s membership in this unique team is more than a little unusual.
But due to the determination of one not-to-be-denied gynecological oncologist, the highly respected Dr. Dianne Miller, Vancouver has become a world- leading centre for ovarian cancer research and a glowing model for a new, cooperative way of doing science.
It all started in 2000 when Miller, a gynecological oncology surgeon at Vancouver Hospital, talked with the son of one of her patients. The man’s mother was dying of ovarian cancer and he wanted to m a k e a d o n a t i o n to research.
“I realized we had nothing coordinated going on,” she says.
“We have known for years that we are ideally suited to do [ collaborative] research in ovarian cancer in Vancouver,” says Miller. “But we were all clinically busy and just didn’t get off our butts to do that. I thought, ‘ Well, it might be time for the rubber to hit the road.’ ”
Miller called a meeting and invited all scientists doing work with ovarian cancer.
They came from UBC, from Vancouver Hospital, from B. C. Women’s and Children’s, and from the B. C. Cancer Agency in Vancouver and Victoria. They filled the room. Many of them had never met.
“There was incredible energy
in that room,” recalls Miller. “It was quite clear that everyone wanted to do it.”
Because Vancouver is a relatively small centre, researchers here have much to gain by working together, says Huntsman, who was at that first meeting.
“In Vancouver we are the right size,” he says. “ A problem like ovarian cancer, we have to work together. It would be really silly for people to be working in isolation. They wouldn’t do as good a work.”
By combining the efforts of surgeons, pathologists, statisticians, and others, Huntsman says they can make their research really count, going from bedside to research bench, to the animal labs and back to the bedside.
The “ Ov Care” team as they have named themselves, (Ov[arian] Ca[ncer]Re[search] Group) has a steering committee of eight and about 40 researchers including YZ Wang, from the B. C. Cancer Agency who has implanted human tumours in mice to create a model for testing. The steering committee is co- chaired by Miller and Huntsman, and includes many senior names in the field.
Among them is Dr. Blake Gilks, a leading pathologist and research scientist at VGH, Dr. Brad Nelson, director of the Deeley Research Centre, the Victoria branch of the BC Cancer Agency who is working on a vaccine and a screening test, and cell biologist Nelly Auersperg at B. C. Women’s and Children’s who, after 25 years in the field, is too excited by her work to retire.
“ These days science is progressing so fast and there is so much new information every week that there is no way you can work in isolation anymore,” says Auersperg.
Ovarian cancer is considered the deadliest of the gynecological cancers. Research, and especially the pap smear screening test, has meant a measurable reduction in cervical cancer deaths while ovarian cancer still kills 80 per cent of its victims — a mortality rate that hasn’t dropped in 50 years.
Ovarian cancer is an ideal candidate for research, says Miller because by the time the ovarian tumours are detected in patients, they are often quite advanced and large. There is lots of tissue left over after the initial pathology work for research.
At the time of the initial meeting, Miller knew the VGH and UBC Hospital Foundation had just completed a successful campaign raising funds for prostate cancer. She convinced them to start a campaign for ovarian cancer. Then she set to work on the B. C. Cancer Foundation.
Like scientists, foundations tend to work alone, intent on protecting and building their institutional identity. But, as Huntsman says, Miller is not one to be denied. Her persuasive energy convinced the foundations to combine their efforts.
The two foundations hope to raise $16 million for ovarian cancer research.
The team realized early on that Vancouver is well- situated to conduct ovarian cancer research. While centres in the United States have more money available to them, Canada has populationcare and socialized medicine, says Huntsman.
“ Across our population everyone gets treated much the same way,” he says. “It’s as if this is a giant clinical trial. We know how everyone has been treated and we know how everyone responded to our treatments.”
But even more valuable is that Vancouver has an incredible resource that nobody else has.
Most hospitals store tissue samples from cancerous tumours for seven to 10 years as required by law. But Vancouver General has been saving tissue samples from every cancerous tumour removed at its facility for the last 50 years.
The team realized that if someone correlated the two data banks, it would create an amazing research tool.
Huntsman set to work. For the last three years he and a four other obsessed scientists have been setting tissue samples on slides and correlating them with all the patient’s data: treatment, outcome, exact pathology, demographics.
They now have about 3,000 ovarian cancer tissue samples in their data bank, called the Cheryl Brown Outcomes Unit after a tireless campaigner for ovarian cancer research who died shortly before the project was completed.
“If someone finds something interesting, they can rapidly test it on 1,000 ovarian cancers with known outcomes and they can say, ‘yeah, this one’s likely to be important or this one you can just trash,’ ” says Huntsman.
Thanks to the human genome project, cancer researchers now know that there are certain mutations or errors in genes that allow the cells to grow out of control. Some are addicted to proteins, some show problems with the RNA, some make the cells grow and some stop them from dying. If they can identify the mutations, they can design therapies that attack those particular errors, says Miller.
Herceptin, a recently authorized treatment for breast cancer, is an example of this type of targeted treatment. Another recently identified mutation is the OPCML gene, which when active suppresses ovarian cancer, but which is turned off in almost 90 per cent of ovarian cancer cases.
“We are just in the infancy of this kind of targeted treatment,” says Miller. “Probably five years from now, almost everybody who gets a cancer will get a battery of tests looking for specific mutations and then get an individualized treatment program as opposed to what we do now, which is give everyone chemo and give some people radiation.”
The Ov Care team has no intention of hoarding their data bank for themselves. Scientists from around the world can test their findings on Huntsman’s tissue samples.
“ If we share them we will learn much, much more,” says Huntsman.
All they ask is that they get credited in the published papers.
Meanwhile, Huntsman and coresearchers in England made a discovery of their own. A mutated gene called EMSY. The mutations in this gene remove the ability of cancer cells to repair their DNA. Its presence in both heredity and sporadic cancers and cancers opens another window for research.
“Our plan is to look at all those cancers to see which ones have the EMSY mutations,” says Huntsman. “Then we can determine whether the presence of these mutations predicts a particular behavior or response to drugs.
Huntsman is excited about the EMSY mutation, but he is more excited about the Ov Care team. Now that the infrastructure is in place allowing research to flourish, now that the door is open to international collaborations, now that the team scientists are set to do the real work, only one piece of the puzzle is missing.
They want a leader, a high profile team player to come to Vancouver and take them into this next stage. To draw someone of the calibre they seek, they need the University of B.C. to establish a chair of ovarian cancer. It’s an expensive need, one the foundations are working on. UBC’s dean of medicine, Dr. Gavin Stuart, a gynecological oncologist, says he is “extremely supportive” of an ovarian cancer chair.
“ I very much hope to see it succeed,” he said in an interview. “It sends a strong message that this i s very much an academic endeavour to move forward with this disease.”
Huntsman hopes that an international conference the team is organizing for May 2006 in Vancouver will draw high calibre medical and science professionals who will see the infrastructure set up here and consider leading the team.
“ If we can make ovarian cancer the easiest cancer for people to study, because all the raw materials are there for them and there is a great clinical team that is really engaged, then more and more basic researchers will start thinking maybe I should turn my attention to this disease,” he says. “ In 20 years’ time when I look back on my career, this is going to be one of the things I am most proud of because I really think it is going to make a difference.”