Medical

Slow-and-steady drug combo wins race against pancreatic cancer

Slow-and-steady drug combo win...
The left image shows clusters of pancreatic cancer cells, while the right image shows cancer treated with the new drug PTC596 (DNA in blue, black are the microtubule structures targeted by the drug)
The left image shows clusters of pancreatic cancer cells, while the right image shows cancer treated with the new drug PTC596 (DNA in blue, black are the microtubule structures targeted by the drug)
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The left image shows clusters of pancreatic cancer cells, while the right image shows cancer treated with the new drug PTC596 (DNA in blue, black are the microtubule structures targeted by the drug)
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The left image shows clusters of pancreatic cancer cells, while the right image shows cancer treated with the new drug PTC596 (DNA in blue, black are the microtubule structures targeted by the drug)

Pancreatic cancer is one of the most deadly forms of the disease, thanks largely to the fact that the tumors tend to be much more solid. This means that cancer drugs aren't able to get inside to work their magic. But now researchers have identified a promising new drug candidate that could linger for longer to worm its way in, and it works especially well when paired with other cancer drugs.

While many cancers are soft and squishy, pancreatic tumors are mostly rock solid, making them particularly troublesome to treat. Unfortunately, that also gives them one of the lowest survival rates of any cancer. Finding new treatment options is a key area of interest for researchers.

To get through that tough tumor shell, cancer drugs may need to be persistent rather than hard-hitting straight away. But of course, that brings its own challenges.

"Pancreatic tumors recruit a thick layer of connective tissue called stroma that hardens the tumor and acts like a shield," says Kenneth Olive, lead author of the study. "As a result, most chemotherapy drugs can't build up to the levels needed to be effective. For a pancreatic cancer drug to be effective, it needs to stick around long enough to seep past the stroma and accumulate in the tumor. But if it is going to persist for a long time in the blood, it can't be as toxic to the rest of the body."

So researchers from Columbia University and the Herbert Irving Comprehensive Cancer Center set out to find just such a chemotherapy drug. A promising candidate was an experimental compound called PTC596, which has previously shown promise against pancreatic cancer in mice and cultured human cells. The drug has been found to stick around for much longer than others and to top it all off, it can even avoid a natural "pump" that cancer cells use to reject substances like drugs.

To test PTC596, the team combined it with another drug called gemcitabine, which is currently used as a first-line drug against pancreatic cancer. This combo was then administered to mice with a type of pancreatic cancer that's particularly aggressive and resistant to chemotherapy.

Sure enough, the double-drug treatment seemed to work, with those mice living three times longer than others treated with just one drug. This is particularly promising because, the team says, it's very rare that any treatment extends the survival time for mice with this kind of cancer.

Better yet, the researchers then added a third drug to the mix and things improved even further. Known as nab-paclitaxel, this drug is also commonly used to treat pancreatic cancer and when combined with PTC596 and gemcitabine, the trio worked to shrink tumors.

Further investigation revealed how PTC596 works. It seems that the drug blocks the formation of microtubules in the cancer cells. This network of proteins is crucial for cell division and transporting nutrients, so blocking it is devastating for the tumors. Interestingly, this is the same mechanism that nab-paclitaxel uses.

"Combining different microtubule inhibitors has the potential to play an important role in the future of oncology, as there are many agents that each impact microtubules in different ways that could produce synergy," says Olive.

The researchers say that PTC596 is a promising candidate for further work, thanks not only to its effectiveness but its safety profile. It may soon end up being administered alongside existing treatments for pancreatic cancer, but as usual there's no guarantee that the results will carry across from mice to humans.

The research was published in the journal Clinical Cancer Research.

Source: Columbia University

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