Proteome of Rare Liver Cancer Sheds New Light on Basic Biology and Ammonia Metabolism

Fibrolamellar tumors cells, pictured here, appear to produce ammonia and contribute to risk of hyperammonemic encephalopathy.

Doctors have long puzzled over a mystery at the heart of fibrolamellar carcinoma, a rare and deadly liver cancer that mainly affects children and young adults. As more common liver cancers, and liver failure itself, fibrolamellar carcinoma can end in an ammonia spike that leads to coma and death. Curiously, however, the conventional methods for treating ammonia spikes in other liver diseases are somehow rendered ineffective in fibrolamellar. Now, new research published on June 21, 2023 in Science Advances may explain this mystery, with findings that suggest fibrolamellar’s ammonia spike is at least partially coming from the tumor itself. By pinpointing the proteins and metabolites unique to fibrolamellar tumors, scientists have also provided new insight into the basic biology and drug sensitivity of these cancer cells. The open-access article is titled “Proteome of Rare Liver Cancer Sheds New Light on Basic Biology.” “We’re seeing a very distinctive change in the proteins of the cancer cells,” says Sanford Simon, PhD, the Gunter Blobel Professor at Rockefeller University. “Our observations help explain some of the physiological changes in fibrolamellar, and also some of the pathological changes—including high levels of ammonia, which is a leading cause of death in fibrolamellar carcinoma.” 

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