Cancer trails dominate $36m funding
Nine researchers will share $36 million from Australia’s top research funding body — its most valuable l grants so far — for work into cancer and other diseases. Lynnette Hoffman reports
NO tears are shed, you won’t find any notes, and no prevention programs are in place, but every second a million of your body’s million billion cells commit suicide. They’re equipped with a built-in self-destruct mode — and while this may not sound like such a good thing, it is.
Cells are prolific breeders and as a million cells die, a million other cells are dividing in two. In a healthy person, the self-destruct mode keeps things balanced. Cancer cells, on the other hand, are practically immortal.
Professor David Vaux of La Trobe University has been studying the intricate process of
cell suicide’’, technically known as apoptosis, since the 1980s. If a gene is damaged in a cell so that it can no longer operate the selfdestruct mechanism, that cell, and all its progeny, will persist, and can eventually turn into a tumour,’’ Vaux says.
By pinpointing those genes that stop cells from killing themselves and searching for ways to switch them off, Vaux and other researchers are closing in on new, hopefully less toxic ways to treat cancer by targeting the specific genes that cause the disease.
The first big break came in 1988 when studying follicular lymphoma, a common cancer of the white blood cells. Vaux discovered that when a gene called Bcl-2 was turned on, the cells couldn’t kill themselves.
‘‘ The damage began with a single white blood cell where two chromosomes broke, but were repaired by the cell the wrong way around,’’ Vaux says. ‘‘ That activated a gene called Bcl-2, and the Bcl-2 protein turned out to be an inhibitor of the self-destruct process — like a pin in a hand grenade,’’ he says.
A drug designed to ‘‘ inhibit the inhibitor’’ is currently in the first phase of clinical trials.
Meanwhile, another family of proteins called IAPs (which stands for inhibitors of apoptosis proteins) have been shown to stop cancerous cells from dying in liver cancer, cervical cancer, some lung cancers and melanoma — and researchers have discovered a protein called Smac that inhibits the IAPs. Several pharmaceutical companies are developing drugs that mimic it.
So far the results are promising. In mice the
‘‘‘‘drugs have caused the cancer cells to selfdestruct, while normal cells have escaped unharmed — although it’s too soon to say whether the drugs will work in people.
There is still masses of research to be done, as scientists have only identified a few of the underlying genetic causes of a tiny amount of cancers. But this week Vaux was awarded a $4 million Australia Fellowship to further his study over the next five years.
The award was one of nine distributed by the National Health and Medical Research Council to fund research in the areas of cancer, infectious disease and mental health. Nearly half of $36 million in funding will go toward the fight against cancer. Professor John Hopper of the University of Melbourne is also looking at the way genes influence cancer — focusing on the way genes make you more or less vulnerable to various environmental risk factors.
Hopper and his colleagues have developed one of the world’s most extensive long-term databases which follows Australians with breast cancer and colorectal cancer, their families, and control groups who don’t have cancer. The data includes blood samples, tissue samples, information on their lifestyles including factors such as smoking and exercise, medication and treatment history.
Hopper’s research has put a hole in the notion that environmental and lifestyle factors have the same impact on disease risk in all people. Depending on your genetic make-up, you may be much more or much less vulnerable to certain environmental factors than someone with a different genetic makeup, Hopper says.
For example, women who have inherited a genetic fault in either of two key breast cancer genes may be twice as likely to develop breast cancer if they smoke cigarettes — but smoking doesn’t seem to increase breast cancer risk in other women who have not inherited a fault in either of the genes.
In other cases, the researchers have found public health benefits they hadn’t expected. For example, oral contraceptives seem to help protect women against breast cancer if they carry a fault in the BRCA1 gene, which increases a woman’s risk of the disease. But for women without the genetic fault, the contraceptives have little or no effect.
Everyone isn’t born equal when it comes to disease risk, especially when it comes to common cancers like those of the breast, bowel and prostate,’’ Hopper says. Knowledge is power and knowing your genetic risk may allow you make better life decisions.’’
The research is also shedding light on the most effective ways to screen people for genetic risks. The norm has been for only people with very strong family histories to be screened — but family history isn’t as strong a predictor as commonly thought. Less than a third of that group carries a genetic fault.
Hopper says it may be more cost-effective to focus on screening people with early-onset cancer instead. Tumour samples can be examined under a microscope to look for telltale signs that the cancer has been caused by a genetic fault. If that’s the case, the patient can then be offered genetic testing. If genetic mutations are indeed found, relatives can be alerted that they may be at a high-risk of cancer as well, and patients can be monitored closely for future cancers, Hopper says.
But ability to predict risks still hinges on researchers developing a better understanding of the genetic aspects of cancers, he says.
Cancer isn’t the only hot topic covered by recipients of the fellowship, however.
La Trobe University’s Tony McMichael is measuring the impact of climate change and environmental influences on public health risks in Australia and abroad.
He says everything from increased cases of salmonella poisoning to increases in death, illness and injury from heatwaves, storms, floods and bushfires are already being documented in Australia.
Mosquito-borne illnesses such as dengue fever are extending further south in Australia, and overseas the effects of climate change on disease are even more obvious.
Malaria is moving to higher altitudes in East Africa and parts of South America, tick-borne encephalitis is spreading north in Sweden as tick populations move north, and cholera is increasing in coastal areas of Bangladesh as the combination of warmer waters and industrial runoff creates a perfect bacterial breeding ground.
Like other recipients, McMichael’s research will also involve developing potential solutions to counteract the problem. Since the climate change genie is already partly out of the bottle, we must also devise ways of adapting and lessening adverse impacts,’’ he says.
Fellowship recipients each receive $800,000 annually over five years.
Boost: La Trobe University’s David Vaux is one of nine research funding winners