"It's like the difference between using a laser-guided missile and carpet bombing. The missile eliminates the target with precision. Carpet bombing kills everything. "
That's senior researchers at the Auckland Cancer Society Research Centre (ACSRC), explaining the difference between chemotherapy and their strategy to attack and destroy lung cancer, head and neck cancer and skin cancer.
The cutting-edge weaponry is Tarloxotinib (TH-4000), their new generation prodrug undergoing phase II trials at 11 clinical sites in the United States and Australia.
ACSRC researchers Dr Adam Patterson and Dr Jeff Smaill have created a unique molecule that can be targeted (think missile) at specific tumours. The "payload" (TH-4000) won't detonate until it's inside a "hypoxic" tumour (those without oxygen in their mass), a form of medical 'stealth technology'.
If it sounds complicated, it is. And, yes, it was very expensive to develop. Just getting to this point has required two decades of world-leading research at ACSRC, with the last 10 years led by Patterson and Smaill.
There was a major step forward last year when UniServices licensed Tarloxotinib to innovative US company Threshold Pharmaceuticals, now funding the phase II testing.
While it's not possible to predict the costs of bringing TH-4000 to market, it commonly takes years and, typically, big pharma estimates up to US$1 billion to do so. But sometimes things speed up in big wars, like the one against cancer.
Most cancer researchers, including Patterson and Smaill, seem genetically predisposed to play down the likelihood of success. But when pushed for a "best, best case scenario" with TH-4000, they almost begrudgingly admit if the phase II trials are successful, TH-4000 could be granted "breakthrough therapy designation," allowing for an expedited review process with the US Food & Drug Administration.
If eventually approved, TH-4000 could be delivering significantly improved treatments to thousands of people, who at present have no other option for these specific types of cancer.
Getting TH-4000 to this point has been a "Herculean" effort; the challenge has been to create a drug that can be delivered into the body, where it sits and waits, until hypoxia arises in a tumour. And then, boom.
World-class researchers, including those at Stanford, Yale and Oxford have worked for many years to discover a drug that will effectively battle hypoxic tumours. Success has proven elusive so far.
"Hypoxia-activated prodrugs are just about the hardest drug design concept on the planet. Our lab is the best in the world at it and has been for decades. If anyone is going to do it, it has to be the ACSRC," according to Patterson and Smaill, who have been working together so long they finish each other's sentences.
These two researchers and their dedicated teams are also involved in multiple "discovery projects" being funded out of America, China and Europe. Best case scenario? "The next iteration of cancer drugs being developed could be bigger than TH-4000."
The ACSRC is managed jointly by the University of Auckland and the Auckland Cancer Society. It was founded in 1956 by the Cancer Society which continues to stump up every year with a large portion of the lab's $12 million annual budget. The rest mainly comes from contestable grants and commercial contracts.
The centre's researchers have punched above their weight for 60 years now. The ACSRC has the distinction of being the first laboratory in the Southern Hemisphere to discover, trial and bring an anti-cancer drug into clinical use.
"All up, we've got 12 cancer drugs into clinical trials, unheard of for a lab of this size (now some 90 researchers, all working on important projects). The next decade may be the most exciting yet, especially in the areas of early detection, precision medicine and immunotherapy," says ACSRC director Prof Bill Denny.
Open Day
The ACSRC is celebrating its 60th anniversary on Saturday, April 9 by hosting an Open Day for the public in the Faculty of Medical and Health Sciences (FMHS) on the University of Auckland's Grafton Campus. More information: www.fmhs.auckland.ac.nz/conquering-cancer