Medical

Existing drug shows promise targeting common cancer mutation

Existing drug shows promise ta...
Mutations in the KRAS gene are associated with pancreatic cancer, but a new study has found a way to fight them
Mutations in the KRAS gene are associated with pancreatic cancer, but a new study has found a way to fight them
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Mutations in the KRAS gene are associated with pancreatic cancer, but a new study has found a way to fight them
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Mutations in the KRAS gene are associated with pancreatic cancer, but a new study has found a way to fight them

Difficult to detect and with a low survival rate, pancreatic cancer is one of the most insidious forms of the disease. But now, researchers have identified an existing drug that could be repurposed to fight pancreatic cancer by targeting a key gene mutation.

Mutations in a gene called KRAS are one of the most common drivers of cancer, and they appear particularly frequently in pancreatic, lung, and colorectal cancers. Unfortunately, KRAS proteins were long considered “undruggable” due to their shape, but recently a drug that can latch onto them has been approved for phase 2 clinical trials.

For the new study, researchers at Virginia Commonwealth University (VCU) have found a new way to attack cancers with KRAS mutations. The team identified four different proteins – CDK1, CDK2, CDK7 and CDK9 – that seem to be expressed in higher levels in tumors that cannot survive without the KRAS mutation, and set about targeting them instead.

To do so, they examined a library of 294 drugs that have already been approved by the FDA for various purposes, and found one that can inhibit all four CDK proteins. The drug, known as AT7519, has so far proven unsuccessful in clinical trials to treat other types of cancer, but it hasn’t yet been tested in pancreatic cancer, the team says.

To test it out, the researchers pitted it against tumors grown in the lab from five pancreatic cancer patients. A7519 successfully suppressed the growth of those cells, and showed similar results in human and mouse mini-organ models. Of course, that's a small sample size and still far removed from in-human tests, but it's an interesting start.

“If our findings are correct and translate in humans, then we should be able to see a positive response in pancreatic cancer patients whose tumors are addicted to mutant KRAS,” says Said Sebti, lead researcher on the study.

If the technique does work, the team says that it might also be applied to other cancers that rely on KRAS mutations, like colorectal and lung cancers.

The research was published in the journal Clinical Cancer Research.

Source: Massey Cancer Center VCU

3 comments
3 comments
Worzel
To progress, they will need funding. Treating cancer, without curing, is far too profitable for that to happen.
Ornery Johnson
As someone who spent 15 years working at the bench doing cancer research, I will add that there are numerous studies each month showing the potential promise of different drugs in model cell lines. Such results must be considered EXTREMELY preliminary, although there is already a trend of combining CDK inhibitors with other known treatments for treating cancers such as Acute Meyloid Leukemia. The good news is that since AT7519 has previously been tested in humans, it should expedite approval of new clinical trials and accelerate Phase 1 (determining the maximum tolerated therapeutic dose.)
Ornery Johnson
Worzel, your point of view is entirely understandable looking from the outside in. There is certainly a lot of money made by pharma, biotech and cancer centers. Still, from the inside I can tell you that during my career I had colleagues tell me they didn't ever think we'd have effective treatments for all forms of cancer because the problem was simply too complex. It's only now that computer algorithms are beginning to help sort out the tens of thousands of protein interactions (signaling events) that occur inside a cell every second that we are beginning to make headway into how to stop the aberrant growth (and death) signals of mutated proteins that cause cancer.