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Cholangiocarcinoma may be the result of a phenomenon that was never thought to be possible, a new study by researchers at the University of California, San Francisco, has found. The study, published in the Journal of Clinical Investigation, shows that the rare liver cancer, which is thought to start in the bile ducts, may develop when hepatocytes transform into biliary cells, says a UCSF press release. This transformation — which was thought to be almost impossible — and the subsequent development of cancerous cells are triggered by the activation of two genes, UCSF says.

Xin Chen and her group accidentally stumbled on the discovery when studying the origins of hepatocellular carcinoma. They activated oncogenes in mice in hopes of making them develop hepatocellular carcinom, and were surprised when the animals developed cholangiocarcinoma instead. "The scientists figured some of the genes they had activated might have reprogrammed the hepatocytes in a way that turned them into aberrant biliary cells, capable of forming tumors," UCSF says. "Their chief suspects were two genes, Notch, which is known to be involved in the embryonic development of bile ducts, and AKT, which has been shown to play a role in many tumors."

The discovery also helps elucidate why people with hepatitis are at a higher risk for bile duct cancer, UCSF says. The researchers are now looking for possible therapeutics, and testing antibodies that may stop the activity of Notch and AKT in mice with bile duct cancers. "If they find the right formula, they may have an answer for a currently untreatable cancer," the press release adds.

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