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ARCHIVED - Personalized medicine for cancer patients

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In future, cancer care that is tailored to the genes and proteins in an individual’s tumour will help physicians to detect cancer earlier and determine how best to treat it in each patient. Personalized cancer therapy could improve survival rates, avoid unnecessary treatment, and reduce health care costs.

It’s not a wonder drug and it benefits less than one-third of all women with breast cancer. But for women with metastatic cancer who over-express a specific gene, Herceptin is a life saver: combined with chemotherapy, it significantly reduces the risk of their cancer returning after surgery, increasing their long-term survival.

Herceptin is noteworthy for another reason. As one of the first examples of targeted molecular therapy, it’s a poster child for the concept of “personalized medicine” — a revolution in cancer care that promises to improve patient outcomes, avoid unnecessary treatments and, ultimately, reduce health care costs.

Unlike broad spectrum chemotherapy drugs, Herceptin is an antibody that blocks a specific cellular protein, called HER2, which is overproduced in the tumour cells of some patients.

The Herceptin story underlines a reality that researchers have known for decades: cancer is not a single disease, but rather hundreds of different diseases. This means that a “one-size-fits-all” approach to cancer treatment would never work. “Cancer is an extremely heterogeneous disease — especially breast and prostate cancer — and heterogeneous diseases require personalized treatment,” says NRC's Dr. Maureen O’Connor.

Every individual’s tumour has a unique “molecular barcode.”

Every individual’s tumour has a unique “molecular barcode.”

Reading your molecular barcode

To some extent, our health care system already personalizes cancer care. “Doctors classify cancers into subtypes and then treat patients according to the category they fall into, although the treatment is rarely based on molecular categorization,” says Dr. O’Connor. But with the development of molecular probes that can detect differences in genes and proteins, it’s becoming easier to classify and treat tumours based on the unique “molecular barcode” of an individual’s tumour.

According to Dr. O’Connor, a personalized approach could influence three major aspects of an individual’s care: their diagnosis, prognosis and treatment. “First, you would ask: do they have cancer?” she says. “Second, you would ask: do they have a good (i.e. slow growing) tumour or a bad (i.e. aggressive) tumour? And third, you would ask: how should we treat their cancer?” In other words, which therapy is most likely to be effective and tolerated by a particular patient?

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Toward a national screening program for lung cancer

Research conducted in the U.S. and Europe suggests that low-dose spiral computed tomography (CT) can significantly lower the risk of dying from lung cancer by detecting the cancer at an early, more curable stage. ?CT scanning is very sensitive. It can detect very tiny abnormalities in the lung,? says Dr. Victor Ling, President and Scientific Director of the Terry Fox Research Institute (TFRI). (More)

Diagnosing lung cancer

Lung cancer is the deadliest form of cancer in Canada — more than 21,000 men and women died from the disease in 2010. Even with the best of health care, less than 20 percent of lung cancer patients survive for five years or more following their diagnosis. The main reason for the low survival rate is that lung cancer is usually diagnosed too late to treat effectively.

In 2008, the Terry Fox Research Institute launched a cross-Canada study that aims to predict which people are at highest risk of developing lung cancer in the next three years, using a combination of medical technology and software. “Preliminary results from the U.S. National Lung Screening Trial show that computed tomography (CT) scanning reduces lung cancer mortality by 20 percent compared to a chest x-ray alone, but the challenge is to identify the right population to screen,” says the BC Cancer Agency‘s Dr. Stephen Lam, who is co-leading the study. “Our main goal is to test a lung cancer risk prediction model to identify which people would benefit most. The ultimate aim is to introduce a cost-effective screening program into the health-care system and to avoid screening low risk individuals where screening may cause net harm.” The study is co-funded by the Canadian Partnership Against Cancer.

Dr. Victor Ling, President and Scientific Director, Terry Fox Research Institute

“The Canadian health-care system now categorizes cancers according to their anatomical sites. In future, we might want to categorize cancers according to their molecular defects.”

– Dr. Victor Ling, President and Scientific Director, Terry Fox Research Institute

Reducing unnecessary treatment for breast cancer

Besides improving diagnosis, a personalized approach to cancer care could reduce the number of patients who receive unnecessary treatment for their disease. For example, “all breast cancers are not the same,” says Dr. O’Connor. “Some women need heavy duty chemotherapy to ensure their cancer doesn’t return following surgery, while other women will be fine with surgery but no chemotherapy.”

To help doctors prescribe the right treatments to the right patients, NRC has developed a tool to determine which breast cancer patients have little risk of their disease recurring. This tool — an algorithm that identifies biomarkers that can predict low risk tumour patients with 87-100 percent accuracy — could virtually eliminate unnecessary chemotherapy and thereby improve the quality of life for low risk patients.

Dr. Edwin Wang is currently applying the algorithm to develop a similar prognostic test for men with prostate cancer.

Lab research at NRC

Lab research at NRC

Targeting tumours

Complementing their work on prognostic tests, NRC researchers are also developing therapeutic antibodies against specific cancer targets. “The main advantage of antibodies as therapeutics is that they are, by definition, targeted — a test that detects the presence of the antibody’s target in the tumour can be done, which allows you to find out on which patients the antibody will likely work,” says Denis Bourbeau, project manager for NRC’s cancer research program. A test of this type is used to identify the one-third of breast cancer patients who are treated with Herceptin.

More on this subject

A prognostic test for prostate cancer

In 2010, an NRC team led by Dr. Edwin Wang announced the development of an algorithm that determines which breast cancer patients have little risk of their disease recurring. With the help of genetic biomarkers, Dr. Wang is now applying the algorithm to predict the prognosis of men with prostate cancer. (More)

In 2009, NRC licensed an antibody that targets clusterin — a protein found in the tumours of some women with aggressive breast cancer — to Montréal-based Alethia Biotherapeutics. “We’ve also licensed a small (protein-like) peptide molecule that could be used for imaging tumours,” says Bourbeau. He suggests that physicians may someday use the imaging peptide to determine if a patient is likely to respond to NRC’s anti-clusterin drug, or if a tumour is shrinking during treatment.

Since every cancer patient is unique, physicians will ultimately need a large number of targeted therapies at their disposal to provide the best possible treatments for everyone. “A drug that works on one breast tumour will not work on all breast tumours,” stresses Bourbeau. But a drug that works on one breast tumour may also work on a brain or colorectal tumour that shares the same molecular barcode.” End