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Vancouver Sun – New B.C. research lays the groundwork for personalized cancer treatment

February 18, 2014

UBC scientists’ advanced gene analysis represents a shift in medicine

By Erin Ellis, Vancouver Sun

Dr. Christian Steidl: ‘We found novel mutations in a gene that have not been described before in any cancer.’

B.C.-based genome research published this week is expected to help doctors target treatment of lymphoma tumours.

“We found novel mutations in a gene that have not been described before in any cancer,” said Dr. Christian Steidl, a scientist at the BC Cancer Agency and a professor in the University of British Columbia’s Department of Pathology who led the study team. “It’s a first description with a state-of-the-art technology.”

Published in the scientific journal Nature Genetics Sunday, the work is part of a worldwide effort to identify gene mutations in all kinds of cancer tumours so treatment can be tailored to an individual’s specific illness.

“That’s what we mean by personalized medicine, that we don’t just use a drug off the shelf and hope it works. That’s what we currently do. We use a drug combination that is very unspecific. It works in a proportion of patients, but we don’t really know why.

“Projecting five to 10 years in the future, this type of research will be the foundation of the shift that will happen in personalized medicine,” said Steidl.

The study took samples from healthy cells and cancer tumours in about 100 patients, which were then analyzed using advanced gene sequencing techniques that have become available in only the last few years. Lead researcher Jay Gunawardana, a PhD student in pathology at UBC, found about 20 per cent of patients with Hodgkins lymphoma and a subtype of non-Hodgkin lymphoma (primary mediastinal B cell lymphoma) carry the same genetic mutation. While there is currently no therapy that can fix the damage caused by this mutation in the gene called PTPN1, experts say it opens the door for other scientists to find a treatment now that the target is known.

The term lymphoma covers about 50 different types of cancer that affect the glands of the lymphatic system that control the body’s immune response. It is divided into two groups, Hodgkin and non-Hodgkin lymphoma, and is the fifth most common cancer type in Canada. Its cause is unknown and it is rising among young adults, according to Lymphoma Canada. Each year, about 8,800 Canadians are diagnosed with lymphoma and more than 3,000 die from the disease.

Dr. Andrew Zelenetz, a lymphoma specialist at Memorial Sloan Kettering Cancer Center in New York who has no connection to the study, said in a telephone interview the discovery is incremental in adding one more piece to the advancement of cancer treatments. But it is a significant contribution to the understanding of lymphoma as diverse rather than a single ailment.

“We often mistakenly think of cancer as one thing, that there will be a single magical cure,” he said. “What genomics has taught us is that we can walk up to three people with the ‘same’ lymphoma, but if we look inside we see it’s three different diseases that should be treated in different ways. Today we don’t have all the treatment tools that we need, but we would like to get away from having to use poisons as chemotherapy. We’d like to get away from drugs that work non-specifically.”

The scale of interest in this area of research can be seen in the International Cancer Genome Consortium which aims to create a catalogue of gene abnormalities found in tumours from 50 different types of cancer. In the U.S., the Cancer Genome Atlas project is focused on specific cancers of the brain, lung and ovary. So far, the missteps in gene coding that cause tumour growth are known in only a tiny fraction of the myriad types of cancer

Dr. Joseph Connors, clinical director of the Centre for Lymphoid Cancer for the BC Cancer Agency, also part of the research team, predicted that a therapy for the particular genetic mutation they described could be developed within three to five years.

“That seems like a long time, but that’s a lot faster than highly effective drugs have been brought into the field for the past several decades.

“This is what I’d call the first and biggest step,” said Connors. “Until we have discoveries like this, we’re essentially shooting blind. We know the cell is malignant, but we don’t know why. We don’t know the biology that’s underlying it.”


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