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Drug Shows Promising Results Against Pancreatic and Breast Cancers

by DailyHealthPost Editorial

When it comes to cancer, researchers are always looking for new effective ways to beat this disease. ProAgio, a drug developed by Georgia State University biology professor Zhi-Ren Liu and his team, is effective at treating pancreatic cancer and prolonging survival in mice, according to a study published in the journal Cellular and Molecular Gastroenterology and Hepatology.

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A second study, published in the Journal of Experimental Medicine, shows the drug is also effective against triple-negative breast cancer, a fast-growing and hard-to-treat type of breast cancer that carries a poor prognosis.

Breaking Down The Cancer Barrier

ProAgio is created from a human protein and works by killing off cancer-associated fibroblasts (CAFs). What are CAFs you ask?

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In cancer-free individuals, fibroblasts are a type of cell that create collagen and other fibrous molecules, and plays a critical role in wound healing.

However, in cancer patients fibroblasts are used by a tumor to create a thick, physical barrier known as the stroma, which protects the cancer and helps it grow. In short, cancer-associated fibroblasts or CAFs for short are simply fibroblasts that have been hijacked by a tumor.

Why Is Stroma a Problem?

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The dense fibrotic stroma is what makes pancreatic cancer, which has a five-year survival rate of just eight percent, so lethal and difficult to treat. Among triple-negative breast cancer patients, research shows denser stroma is associated with poorer survival and high recurrence rates.

“All solid tumors use cancer-associated fibroblasts, but in pancreatic cancer and triple-negative breast cancer, the stroma is so dense there’s often no way for conventional drugs to penetrate it and effectively treat the cancer,” said Liu.

Stroma’s Secondary Function: Stealth

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The stroma also helps the tumor hide from your body’s immune system. Immunotherapy, a type of treatment that uses your immune system to fight cancer, is less effective against tumors protected by a dense stroma that is rich in cancer-associated fibroblasts.

Only Killing The Bad Guys

The ProAgio drug is unique in that it targets only CAFs cells that are actively engaged in supporting cancer rather than inactive fibroblasts. This reduces side effects of the drug and increases its effectiveness.

“When you have a wound, for example, normal fibroblasts will secrete fibers to limit the damage and promote healing,” said Liu. “The tumor region is basically a wound that won’t heal. Quiescent fibroblasts may play a role in preventing cancer from spreading. You don’t want to kill the good guys, only the bad guys.”

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ProAgio is licensed to ProDa BioTech, a pharmaceutical research company founded by Liu. In 2018, ProDa BioTech received $2 million from the National Cancer Institute to fund toxicology and pharmacokinetic studies that are required before moving the drug to early-stage clinical trials.

Those studies have now been completed and the company has submitted an Investigational New Drug (IND) Application, a request for authorization from the Food and Drug Administration to administer ProAgio to human subjects.

Once the IND is granted, Liu says the immediate next step is to begin clinical human trials. The first trial will begin in early 2021 at the National Institute of Health Clinical Center in Bethesda, Md.

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