Genetic study of liver cancer reveals a new drug target


Histological pictures of aggressive liver tumors obtained from transgenic mice (by injection of tail veins of transposable genetic elements) with MAGEA3-induced overexpression. Credit: Craig AJ et al., 2021, PLOS Genetics

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 deaths 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 on Mount Sinai and his colleagues.

Scientists have previously discovered several genes that drive the growth of HCC tumors, although the benefits of treatment with approved drugs are still limited. In the new study, Villanueva and colleagues collected 44 tumor biopsies from 12 patients with HCC. The researchers used RNA sequencing to study which genes were most highly expressed in regions of a high grade of a tumor compared to regions of the same grade. .

A family of genes: testicular antigens (CTAs) were recurrently expressed in the most aggressive regions of tumors. CTAs, most of which are found on the X chromosome, are generally expressed in male germ cells within the testicles and are thought to play a role in spermatogenesis, in addition to protecting by stressors and cell death. Villanueva’s team found that CTAs, and especially MAGEA3, are associated with a poor prognosis in HCCs. In addition, when the group blocked MAGEA3 expression in cells isolated from HCC, 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 more quickly. Future studies are needed to replicate the results in larger patient populations and to check whether MAGEA3 itself or its subsequent targets are more effective for therapeutic targeting.

“The study discovered the role of testicular cancer antigens, specifically MAGEA3, in the progression of liver cancer,” Villanueva adds. “Demonstrates how selective inhibition of MAGEA3 has antitumor effects in experimental models of this disease. In general, the study provides the principle test for testing MAGEA3 inhibition in the early stages for patients with primary liver cancer “.

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More information:
Craig AJ, Garcia-Lezana T, Ruiz de Galarreta M, Villacorta-Martin C, Kozlova EG, Martins-Filho SN, et al. (2021) Transcriptomic characterization of testicular cancer antigens identifies MAGEA3 as a driver of tumor progression in hepatocellular carcinoma. PLoS Genet 17 (6): e1009589.

Citation: Liver Cancer Genetic Study Reveals New Drug Target (2021, June 24) Retrieved June 24, 2021 at reveals-drug.html

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