Genetic study of liver cancer reveals new drug target – sciencedaily

Drugs targeting the MAGEA3 gene may help block the growth of hepatocellular carcinoma (HCC), the most common type of primary liver cancer and one of the leading causes of cancer death in the country. This is one of the conclusions of a new study analyzing the genetics of HCC tumors published on June 24 in the journal PLOS Genetics by Augusto Villanueva of the Icahn School of Medicine of Mount Sinai and his colleagues.

Scientists have already discovered several genes that cause HCC tumors to grow, but the therapeutic benefits of approved drugs are still limited. In the new study, Villanueva and his colleagues collected 44 tumor biopsies from 12 patients with HCC. The researchers used RNA sequencing to study which genes were more highly expressed in high-grade regions of a tumor compared to low-grade regions of the same tumor.

One family of genes – testicular cancer antigens (CTAs) – has been overexpressed over and over again in the most aggressive regions of tumors. ACTs, most of which are located on the X chromosome, are typically expressed in male germ cells in the testes and are believed to play a role in spermatogenesis as well as protecting germ cells from stressors and cell death. Villanueva’s team found that ACTs, and in particular MAGEA3, are associated with a poor prognosis in HCC. In addition, when the group blocked expression of MAGEA3 in isolated HCC cells, the cells could no longer proliferate and eventually died. When the group overexpressed MAGE3 in the liver cells of HCC-prone mice, the animals died of cancer faster. Future studies are needed to replicate the results in larger patient populations and to determine whether MAGEA3 itself, or its downstream targets, are more effective to target therapeutically.

“The study uncovered the role of testicular cancer antigens, in particular MAGEA3, in the progression of liver cancer,” adds Villanueva. “This demonstrates how selective inhibition of MAGEA3 has anti-tumor effects on experimental models of this disease. Overall, the study provides the proof of principle to test inhibition of MAGEA3 in early phase clinical trials for patients with primary liver cancer. “

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