Genetic insights into cancer

by Margo White / 21 July, 2012
Genetics gives researchers a new weapon in the war on the Big C.


In 1971, the Nixon Administration declared war on cancer, proclaiming that the disease would be beaten within a decade. Those were optimistic days, when scientists didn’t know that cancer wasn’t one disease, but a variety of disorders with myriad idiosyncratic mutations that can combine in an infinite number of ways. “Just as our fingerprints are unique, so are cancers,” says University of Otago cancer researcher Anita Dunbier. “That’s what makes it so hard to fight … To say we want to find a cure for cancer is like saying we want to find a drug to cure every possible type of infection.”

This might present cancer researchers with an impossible task. On the other hand, as genetic sequencing can today be done for a fraction of the cost of a decade ago, and more quickly than was imaginable back then, there is a renewed hope that, by focusing on cancer genomes, scientists will find better cures for more types of the disease. This has already resulted in targeted therapies aimed at particular genetic changes. Herceptin, for instance, is the first targeted therapy for breast cancer. “It’s a very exciting time in cancer research,” says Dunbier. “The first human genome took nearly 15 years to be sequenced and cost over US$3 billion. Now, at Otago, we do it in 10 days for around $3000. For understanding cancer, that’s a really big help.”

Dunbier’s own genetic insights into breast cancer made headlines in the UK last year, when she was working at the Institute of Cancer Research in London. She identified three new genes that might explain why some women with hormone-dependent breast cancer, or ER-positive cancer, don’t respond well to drug treatment. Hormonal cancer accounts for 75% of breast cancer tumours, and patients are usually treated with a class of drugs known as aromatase inhibitors, such as Anastrozole, that block the production of oestrogen. By genetically profiling the tumours of 104 post-menopausal women with hormonal breast cancer before and after Anastrozole treatment, Dunbier and colleagues found that when these three genes were switched on, the drug was less effective.

Dunbier, who was awarded a fellowship from the Health Research Council, has established a breast cancer research group at the University of Otago’s Centre for Translational Cancer Research. She is studying how these newly identified genes function, how they influence the rate of tumour growth and exactly why they seem to interfere with drug therapy. This could lead to new therapeutic targets. However, aware that new drugs take years to develop, Dunbier is also investigating the way a particular immune response to those oestrogen-blockers benefi ts the tumour at the expense of the host. Her yet-to-be-tested hypothesis is that dampening down the immune response with common antiinfl ammatories could improve the oestrogen-blockers’ effectiveness. She is also looking for ways to harness molecular tools to better identify when certain treatments might be a waste of time. Chemotherapy, for instance, is an expensive, unpleasant and sometimes risky treatment commonly prescribed for women with breast cancer, but it isn’t always useful.

In the US there is a widely used but expensive test to identify patients for whom chemotherapy would be ineffective. Dunbier was part of a large study in the UK that resulted in the development of a cheaper version using a procedure called immunohistochemistry. “It’s not widely used in New Zealand, but we’re working on it.” As Dunbier notes, personalised medicine (some would call it precision medicine) doesn’t only involve the development of new therapies, but a more informed use of those that exist. “Rather than throwing a whole bomb at something in the hope that something will work, you can have a laser-guided missile for a target that you know is there.”

BOTOX REDUCES TREMORS


Botox may help prevent shaking or tremor in the arms and hands of people with multiple sclerosis, according to a study in Neurology. Researchers at Royal Melbourne Hospital gave 23 MS sufferers either botulinum toxin injections or a saline placebo for three months; they were then given the opposite treatment for the same period. When participants received botulinum toxin, the tremors changed from moderate to mild, and their writing and drawing improved by an average of one point on a 10-point scale.

ARTHRITIS GENES FOUND


The largest genome-wide association study of osteoarthritis, led by Newcastle University researchers, has found eight new genetic variants that appear to increase susceptibility to osteoarthritis, which affects about 40% of over-70-year-olds. The findings bring to 11 the total number of osteoarthritis susceptibility genes that have been isolated in European populations.

STRAWBERRIES TO THE FORE


Blueberries have hogged the headlines in recent years, but scientists at the University of Warwick are highlighting the beneficial effects of strawberries. The researchers discovered strawberry extracts activate a protein called Nrf2 that reduces blood lipid and cholesterol, that if elevated can lead to cardiovascular problems. Eating strawberries has previously been found to counter low-density lipoprotein, or “bad” cholesterol. But this is the fi rst time strawberry extracts have been proven to actively stimulate proteins that protect against disease. Researchers will next try to identify the strawberry varieties that have the greatest effect, how they are best served and how many we need to eat.
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