Change the AMP945 to the drugs new name … narmafotinib and away you go
Enjoy…
Beating the pancreatic cancer odds
A new drug, known as AMP945, is a possible game changer in the battle against one of our most deadly cancers.
Here’s how it works.It was the worst possible news. When Chris Baggoley discovered he had pancreatic cancer, he knew better than most just how bad the odds were.
An emergency doctor by training, Baggoley had risen to the top of his profession — he served as the nation’s chief medical officer for five years — but all the medical knowledge in the world cannot prepare you to confront your own fate.
“You can’t spend all the time as I have in medicine and expect that you’re any different to anybody else,” Baggoley says. “Textbooks are full of diseases and descriptions of them, and it’s just the human condition for us all to get something at some stage. I didn’t spend time thinking ‘why me?’.”Baggoley’s diagnosis came by chance.
His blood counts had been dropping across a period of several years. His haematologist, attempting to get to the bottom of why, was concerned by the extent of his patient’s weight loss, and ordered a CT scan of Baggoley’s abdomen.
When the scan revealed pancreatic cancer, Baggoley had no symptoms at all.
A lack of symptoms is not unusual in pancreatic cancer and it’s one of the reasons the condition that recently killed US Supreme Court associate justice Ruth Bader Ginsburg is usually diagnosed late, when the chances of survival are much narrower.
The deadliest of all cancers, only 20 per cent of those with pancreatic cancer are still alive 12 months after their diagnosis. The five-year survival rate is only 11 per cent and has barely budged in the past two decades.I feel very lucky that I was diagnosed early,” Baggoley says.
I have been blessed with having world’s best treatment for pancreatic cancer, which might make the difference, and make a big difference. But what I know is that with other cancers you have the first line of treatment, then you can go to other lines of treatment.
That’s not the case with pancreatic cancer.”Baggoley’s treatment consisted of a type of surgery known as a Whipple’s procedure, in which the affected part of the pancreas is removed together with part of the small intestine and the bile duct.
He then underwent six months of chemotherapy. One year and nine months on from his diagnosis, there is now no evidence of cancer in his body.
But for many patients with pancreatic cancer, there’s a major impediment to chemotherapy drugs’ ability to attack cancer cells.
Doctors treating patients with pancreatic cancer have the challenge that the cancer is often protected by a layer of scar tissue caused by a process known as fibrosis.
Also known as fibrotic scarring, fibrosis is the development of fibrous connective tissue, and it’s important in providing structural integrity to many organs in the body and in healing after injury.]
However, when fibrosis is uncontrolled, it can result in a build-up of stiff scar tissue that can prevent organs in the body from functioning properly, causing disease.
Many cancers also form a fibrotic tissue shield to protect them from the immune system and, unable to penetrate this shield, chemotherapy drugs are hindered in their ability to treat the cancer.
In the past five years there has been renewed interest in switching off the particular protein, known as focal adhesion kinase, that controls the formation of the protective fibrotic layer around cancer cells that inhibits the penetration of chemotherapy drugs.
Pancreatic cancer is well-known for having this fibrotic shield.
Working together under the Cancer Therapeutics Co-operative Research Centre, scientists from the nation’s top universities, the Peter MacCallum Cancer Centre, the Walter & Eliza Hall Institute of Medical Research and Cancer Council Victoria, among other organisations, have made a breakthrough.
They’ve invented a new drug, known as AMP945, which targets the FAK protein, potentially enabling the drug to treat and prevent fibrotic diseases, as well as make cancers that previously were resistant to treatment responsive to chemotherapy.
Mark Devlin is a key scientist who worked on the development of AMP945.“FAK can help cancer form a protective or fibrotic scar-like layer, and it stops cancer drugs and any cancer immune cells from reaching the tumour,” Devlin says. “
The other thing that FAK can do is it can act as a survival switch for cancer cells. It switches on the activity of the protein and that contributes to the formation of the protective layer.“Turning off that switch with AMP945 may make the cancer cells easier to kill.
So it’s really a dual attack.”After encouraging results in animal models, AMP945 soon will begin clinical trials in Australia. It’s a significant step given that very few drugs invented by Australian scientists onshore make the leap from research discovery to the beginnings of commercialisation.Melbourne-based biotechnology company
Amplia Therapeutics is commercialising the drug, which will soon begin the first phase of clinical trials, and is hopeful that AMP945 could make it all the way to the market.“
There’s been lots of good scientific research going on for decades in Australia, but the bit that we’ve struggled with is the transition of drugs across what we sometimes call in the industry the valley of death,” Amplia Therapeutics chief executive John Lambert says. “
That’s the gulf between the discovery of a molecule that looks interesting, and its entry into clinical trials and passage all the way through to approval.“There’s a lot of really good science goes on in labs all over Australia, but it’s rare for the fruits of that collaboration to actually end up in a molecule that ends up in a clinical trial.“
There are so many things that can go wrong along the way, not all of them scientific. But we’re very excited by the prospects of this drug, we think it offers the potential to be a game changer in pancreatic cancer and fibrosis.
Now we need to do the trials to see if that’s actually true.” As the drug begins clinical trials, nationally, a roadmap is being developed for pancreatic cancer that it is hoped will be the first step on the road to improving survival rates.Cancer Australia chief executive Dorothy Keefe says the roadmap will be important to lifting the profile of pancreatic cancer.“
Pancreatic cancer is a cancer with very poor outcomes historically and even though they’re improving, they’re improving so slowly that people with pancreatic cancer are feeling left behind,” O’Keefe says.“
One of the problems in pancreatic cancer is that the five-year survival has only gone up over the last 20 or 30 years to about 11 per cent, which is pretty bad. That actually means that you only have a very small number of long-term survivors, whereas with other cancers where we have made great progress we have many long-term survivors, and the more long-term survivors there are, the higher profile you can have.”
Cancer Australia is calling for contributions to its consultation hub for the pancreatic cancer roadmap. As efforts to combat the disease gather pace, Cancer Therapeutics CRC continues to invest in cutting-edge therapies.
The CRC was established in 2007 and has received $71m in federal funding to develop new small molecule cancer therapeutics. The centre was established with the express intent of bridging the gap between the discovery of new drugs and the commercialisation of those drugs.Devlin, who previously worked as the CRC’s director of translational biology and is now the chief scientific officer for Amplia Therapeutics, says long-term significant funding has been crucial.“Drug discovery has very long timelines and that sort of period of funding,
I believe, is what is required to make serious inroads into establishing drug discovery in Australia,” he says.“The reality is that there are very few superstars in drug discovery.
It’s the ultimate scientific team sport. You really need diverse scientific skills to come together in order to generate effective drugs.“
The CRC has been an opportunity for scientists to establish careers in drug discovery. And that’s always been something that’s been quite difficult in Australia. We don’t have the depth of drug discovery companies and biotech that, say, the US and Europe have. So having that federal government support for an extended period … has allowed Australians through the CRC to really establish some of those capabilities.”
Getting AMP945 into clinical trials is not the only coup for the Cancer Therapeutics CRC. It has recently signed preclinical deals for two of its other small molecule drugs to big pharmaceutical companies Pfizer and Merck.
One of the deals has the potentially to bring $460m in to Australia.“The collaborative structure has been such a big success and this shows us what happens when our leading research institutes are given the means and resources to collaborate,”
Cancer Therapeutics acting chief executive Lisa Dube says.For Baggoley, early detection of pancreatic cancer is just as key as new treatments. “
Certainly I think we need two things with pancreatic cancer,” he says. “One is something to identify its development early so that more people are diagnosed before it has spread.“
Then the second thing is to learn more about why pancreatic cancer is traditionally resistant to even the most advanced cancer therapies.“I think what we know is that pancreatic cancer is resistant to the most advanced cancer therapies, so any research that can make a difference to making pancreatic cancer being accessible to chemotherapy is a really valuable and most important advance.”
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