Australian researchers seem to have scored a first in the genetic sequencing of pancreatic cancer. This could be the first step towards developing personalised cancer treatments.
It is almost exactly two years since cancer researchers from 24 countries came together and agreed to catalogue the genetic changes involved in the 50 most common cancers.
AdvertisementProfessor Andrew Biankin, head of pancreatic cancer research at the Garvan Institute of Medical Research in Sydney, hailed the breakthrough as marking a new era in cancer research and said, "By understanding and looking at the map of what makes these cancers different, we can understand more about the cancer. We can, in the future, start to direct specific treatments for specific cancer, really heralding an age of genetically guided personalised medicine. "
Interestingly whil it took thousands of people around the world 15 years and more than $1.5 billion to sequence the human genome, it might not take that long to unlock the genetics of cancer, said Ashley Hall, reporting ABC radio.
Professor Biankin said, "We can do it within a week and for a lot, lot less than that. And we can do it at a scale which doesn't take a company and multiple governments to do it. It can be done in one laboratory."
The Australian Pancreatic Cancer Genome Initiative is the Australian project arm of an association of research organisations in 11 countries, known as the International Cancer Genome Consortium. Their collective aim is to catalogue 25,000 full genomes of the 50 most common types of cancer and make the data freely available online.
"It's an extraordinarily devastating disease," says Dr Andrew Penman, head of the Cancer Council of NSW. "Each year around 1900 people are diagnosed in Australia. Almost all of those are dead within the year, and only 5 per cent live beyond five years of diagnosis."
This makes pancreatic cancer the eleventh most common cancer in Australia, but fourth most likely to cause death. These figures have not improved in more than 30 years.
Professor Sean Grimmond from the Institute of Molecular Bioscience in Brisbane, collaborating with Professor Andrew Biankin, said, "The question we are asking is: What goes wrong in pancreatic cancer itself?" says Grimmond, who is in charge of the gene sequencing side of the work. And the promise of the answer is personalised medicine for every cancer patient.
All cancer cells have a huge number of abnormalities and no two cancers are the same - even within the same cancer type. The key is identifying those abnormalities that are unique to cancer biology.
The research involves sequencing two genomes for each patient. The three billion bits of normal cell DNA is compared with the pancreatic cancer cell DNA to identify the damage in the tumour that leads to cancer growth.
Today, Australia and three other members of the ICGC are the first to publish results online at www.icgc.org. Australia has sequenced two pancreatic cancer genomes, alongside Britain (breast cancer), Japan (liver cancer) and China (gastric cancer). "That is the proof of principle to show it can be done," says Grimmond. "We're still in our first year and the next seven patients' tumour samples are well under way."
"Currently we're looking at doing 25 patients in the first year and it's conceivable that within a couple of years we could be sequencing a genome a week and doing the analysis in a similar period of time," Grimmond says.
"We need to have about 100 tumour sequences for the first experiment to really work out what drivers are promoting cancer and what genes have been lost that would normally prevent cancer." From a patient perspective, this means that practical results could be seen within two or three years.
"The first thing we will be able to do is use a particular treatment for pancreatic cancer that might already be used for another cancer that has the same set of mutations," says Biankin. This will sidestep the years and millions of dollars it would otherwise take to do traditional clinical trials.
"If we know a particular drug works in patients with particular mutations for say, glioblastoma [a brain tumour], then we should trial that drug in pancreatic cancers with those same mutations. There have been at least 50 trials in pancreatic cancer of a significant input in energy and size over the last 20 or 30 years, using the old methods and technologies, and most of them have been negative."
The second step is to harness the new age of anti-cancer drugs for pancreatic cancers that target specific abnormalities in pancreatic cancer genes. The aim is for patients to have their full cancer genomes routinely sequenced as part of their diagnosis and treatment plan.
"We want to take the guesswork out of chemotherapy," says Grimmond. "When a patient presents with a tumour, we want to be able to sequence it and say don't use this drug, use that drug because we know that this tumour will be resistant to drug A, but may be susceptible to drug B."
For a pancreatic cancer patient, it is critical to get the treatment right the first time. "By the time we get to the treatment that's going to work, it might be third or fourth down the line and the cancer may have advanced," says Biankin. "In the case of pancreatic cancer, the patient has probably died."
The longer-term aim for researchers - over 20 years - is to apply the understanding of differences between individual pancreatic cancers at a genetic level to design drugs to specifically target each one of those molecular genetic abnormalities. This will herald the era of personalised prescriptions based on each patient's individual cancer genome.
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