Pancreas or pancreatic cancer

 Scientists researching a cure for pancreatic cancer reveal 'breakthrough'

 [ Pancreatic cancer patients could benefit from a new treatment in the future. ]

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."

Pancreas or pancreatic cancer with organs and tumors or cancerous cells 3D rendering illustration with male body. Anatomy, oncology, disease, medical, biology, science, healthcare concepts.

[ Pancreatic cancer rarely causes symptoms in the early stages, so often isn't detected until an advanced stage. ]

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.

Unhappy woman stomach ache, mature woman with stomach pain feeling unwell sitting in living room

Later pancreatic symptoms might include pain the stomach or back, jaundice and weight loss. (Getty Images)

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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Israeli scientists find way to treat pancreatic cancer in 14 days.

The tumor in one mouse that was injected with human cancer cells completely disappeared.

DECEMBER 6, 2019 

Cancerous cells forming a lump in the pancreatic tissue

A new treatment developed by Tel Aviv University could induce the destruction of pancreatic cancer cells, eradicating the number of cancerous cells by up to 90% after two weeks of daily injections of a small molecule known as PJ34.

Pancreatic cancer is one of the hardest cancers to treat. Most people who are diagnosed with the disease do not even live five years after being diagnosed.

The study, led by Prof. Malka Cohen-Armon and her team at TAU’s Sackler Faculty of Medicine, in collaboration with Dr. Talia Golan’s team at the Cancer Research Center at Sheba Medical Center, was recently published in the journal Oncotarget.

Specifically, the study found that PJ34, when injected intravenously, causes the self-destruction of human cancer cells during mitosis, the scientific term for cell division.

The research was conducted with xenografts, transplantation of human pancreatic cancer into immunocompromised mice. A month after being injected with the molecule daily for 14 days, “there was a reduction of 90% of pancreatic cells in the tumor,” Cohen-Armon told The Jerusalem Post. “In one mouse, the tumor completely disappeared.”

“This molecule causes an anomaly during mitosis of human cancer cells, provoking rapid cell death,” she said. “Thus, cell multiplication itself resulted in cell death in the treated cancer cells.”

Moreover, she said, PJ34 appears to have no impact on healthy cells, thus “no adverse effects were observed.” The mice, she said, continued to grow and gain weight as usual.

She added that she first published about the mechanism in 2017 when it was used to effectively treat triple-negative breast cancer implanted in xenografts. This type of breast cancer – which tests negative for estrogen receptors, progesterone receptors and excess HER2 protein – like pancreatic cancer, is very hard to treat and many women don’t live more than five years after being diagnosed.

Though Cohen-Armon said the team did not specifically study whether or not the treatment could prolong the lifespan of a patient, one can assume such an effect could result if the cancerous cells are eliminated.

How long will it take to move from mice trials to human trials?

She estimates that would take “at least two years on the condition that we get enough funding.”

First, she said, the group will test the treatment on pigs and then apply for permission from the FDA to administer humans with this molecule.

“I am optimistic,” Cohen-Armon concluded.