Stem cell gene targeted to treat drug-resistant pancreatic cancer

cancer cells
Cancer cells--Courtesy of National Cancer Institute

UC San Diego researchers have identified the stem cell gene Musashi (Msi) as a potential target to treat deadly pancreatic cancers. It can be targeted directly to halt tumor growth, or used in real-time imaging to tackle drug resistance in pancreatic tumors.

With a 5-year survival rate of 6%, the most common pancreatic cancer, pancreatic ductal adenocarcinoma, is also one of the deadliest. Chemotherapy is often ineffective due to the pancreas’ location deep within the abdomen and pancreatic tumors’ high rate of resistance to currently used drugs.

The UC San Diego team, alongside colleagues from the University of Nebraska, Japan’s Keio University and Carlsbad, CA-based Ionis Pharmaceuticals, created new “reporter” mouse models to allow for the noninvasive, image-based tracking of stem cell signals in live animals. They discovered the expression of the stem cell gene Musashi (Msi) rises as pancreatic cancer progresses, and that Msi-expressing cells spur cancer growth, drug resistance and lethality.

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The investigators developed antisense oligonucleotide (ASO) inhibitors that targeted and blocked Msi-expressing cells, which arrested tumor growth in animal models as well as in cancer cells obtained from patients. ASO inhibitors work by selectively binding to messenger RNA from the chosen disease-linked gene and inactivating it.

Targeting Msi in primary tumors changed “the trajectory of progression,” inhibiting both cancer stem cells and other tumor cells, said Tannishtha Reya, a professor in the Pharmacology and Medicine departments at the UC San Diego School of Medicine, in the statement. The researchers are hopeful that Msi antagonists could be a new strategy to target chemotherapy-resistant tumors.

And that’s not all.

“Because Msi reporter activity can be visualized by live imaging, these models can be used to track cancer stem cells within the tumor microenvironment, providing a real-time view of cancer growth and metastasis, and serving as a platform to test new drugs that may be better able to eradicate resistant cells,” Reya said.

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