Scientists researching a cure for pancreatic cancer reveal 'breakthrough'
Scientists have designed a candidate drug (a molecule with strong therapeutic potential) that could help make pancreatic cancer a treatable and potentially curable condition, according to new research.
While less common than other types, pancreatic cancer – found anywhere in the pancreas, an organ in the top part of your tummy – can be hard to treat and cure.
The new molecule permanently modifies a cancer-causing mutation called K-Ras G12D, responsible for nearly half of all pancreatic cancer cases and also appears in some forms of lung, breast and colon cancer.
"We've worked for 10 years to bring pancreatic cancer therapies up to speed with therapies for other cancers," says Kevan Shokat, a professor in the Department of Cellular and Molecular Pharmacology at the University of California who led the work, with findings published in Nature Chemical Biology.
"This breakthrough is the first to target G12D and gives us a firm foothold to fight this devastating mutation."
Shokat and his colleagues developed the first cancer drugs to stop a different K-Ras mutation, G12C, in 2013. Since then, two therapies have been approved for use in lung and breast cancer, but pancreatic cancer was still left in the lurch.
K-Ras mutations are extremely common in pancreatic cancer (explaining 90% of cases), of which half are G12D, different to other types by a single amino acid change.
The slight difference between healthy and cancer-causing proteins presented a huge challenge for chemists. "To make good therapies, we need drugs that work on the tumour cells only, without affecting healthy cells."
On the latest discovery, Shokat adds, "Once we had that structure for our molecules, we knew they were sitting in the protein at the right spot. Then we could explore the little nooks and crannies that we needed to discover the chemistry of the aspartate [one type of amino acid]."
The scientists went through dozens of chemicals. "It's like climbing a new route on a mountain, you may be strong but the lengths of your arms limit what you can do. It was a lot of trial and error, tweaking the branches of these molecules to position them in this incredibly tight space around G12D. Some got close, then failed, and we would start over."
Eventually, they found the winning molecule that 'settled into the appropriate corner of K-Ras and bent into a new shape that reacted strongly with the aspartate'. In short, this means the molecule halts tumour growth from G12D in cancer cells, as well as an animal model of human cancer, while never attacking healthy proteins.
The scientists are now working on making the molecule durable enough to fight cancer in the human body. With the traction of this study, Shokat said new therapies for pancreatic cancer could enter clinical trials in as little as two to three years.
"We've learned a lot from other targeted therapies and know how to quickly translate discoveries like these for the clinic," says Margaret Tempero, MD, director of the UCSF Pancreas Center. "An effective drug targeting K-RAS G12D could be transformative for patients with pancreatic cancer."
In light of this research, Dr Chris Macdonald, head of research at Pancreatic Cancer UK, says, "We desperately need more treatment options for pancreatic cancer that are effective at destroying cancer cells without causing significant side effects. KRAS mutations are known to be the main driver of pancreatic cancer, making them a promising target for new treatments.
"By specifically targeting changes in cancer cells, this therapy has the potential to block tumour growth without impacting healthy cells, which could prevent harmful side effects that are experienced as a result of many cancer treatments. This research is still in the early stages but if future work proves successful, this therapy could be a promising new treatment option for pancreatic cancer."
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Watch: Video uses voices of celebrities who died of pancreatic cancer to raise awareness
