Researchers Discover a Culprit Behind Aggressive Liver Cancer

Patients whose disease contained the osteopontin protein tended to have more aggressive liver cancer that did not respond to treatment.

Researchers found a protein in liver cancer that can make it more aggressive and not respond to therapy. Their findings, which were recently published in the Journal of Hepatology, may lay the groundwork for broadening the group of patients with liver cancer whose disease can be treated with immune checkpoint inhibitors.

The study explained that as cancers became more heterogenous – meaning that there are many diverse mutations and therefore different proteins in the disease – they became more aggressive, leading to worse outcomes for the patient.

“Patients with short survival times tend to have more heterogenous tumors than those who have more simplified tumor composition,” study author Xin Wei Wang, deputy chief of the Laboratory of Human Carcinogenesis, said in a statement.

Wang, who holds a postdoctoral degree, and his colleagues analyzed 46 tumor samples from patients with hepatocellular carcinoma (HCC) and 37 samples of intrahepatic cholangiocarcinoma (iCCA). They found that when tumors contained a protein called osteopontin, they tended to have higher tumor heterogeneity. The researchers theorized that somehow, oestopontin may help tumors to evade treatment.

“In patients who are not responsive to treatment, this protein is elevated,” Wang said. “So functionally, this protein may be acting as the driver to make the tumor cells more likely to escape from treatment.”

Of note, researchers have been struggling to find a way to understand why some patients with liver cancer have disease that does not respond to immune checkpoint inhibitors, or that responds and then stops responding.

“If we have a therapy that blocks osteopontin, in combination with a checkpoint inhibitor, presumably we can increase the treatment efficacy,” Wang said.

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