eIF4A1 Is a Prognostic Marker and Actionable Target in Human Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC) is a primary liver tumor with high lethality and increasing incidence worldwide. While tumor resection or liver transplantation is effective in the early stages of the disease, the therapeutic options for advanced HCC remain limited and the benefits are temporary. Thus, novel therapeutic targets and more efficacious treatments against this deadly cancer are urgently needed. Here, we investigated the pathogenetic and therapeutic role of eukaryotic initiation factor 4A1 (eIF4A1) in this tumor type. We observed consistent eIF4A1 upregulation in HCC lesions compared with non-tumorous surrounding liver tissues. In addition, eIF4A1 levels were negatively correlated with the prognosis of HCC patients. In HCC lines, the exposure to various eIF4A inhibitors triggered a remarkable decline in proliferation and augmented apoptosis, paralleled by the inhibition of several oncogenic pathways. Significantly, anti-growth effects were achieved at nanomolar concentrations of the eIF4A1 inhibitors and were further increased by the simultaneous administration of the pan mTOR inhibitor, Rapalink-1. In conclusion, our results highlight the pathogenetic relevance of eIF4A1 in HCC and recommend further evaluation of the potential usefulness of pharmacological combinations based on eIF4A and mTOR inhibitors in treating this aggressive tumor.

Role and Elevating Prognostic Precision of Pivka-Ii as a Superior Biomarker in HCC Diagnosis, Surpassing Afp

“…Its frequency is 6.8 per 100,000 in America, 5.5 per 100,000 in the west coast of Europe, and it increases up-to seventeen percent in Asia (Koulouris et al, 2021). According to the World Health Organization, liver cancer is becoming more common, and by 2030, it is expected to be responsible for over one million fatalities per year (Steinmann et al, 2023) .The majority of HCC cases are the result of prolonged liver damage induced by the hepatitis type B or C virus. Cirrhosis of the liver, of any cause, is adeterminant for causing liver Carcinoma (Prabhakar et al, 2023).…”

Editorial for the Special Issue—“Recent Advances of Novel Pharmaceutical Designs for Anti-Cancer Therapies”

“…The specific targeting of the translation machinery of proliferating tumor cells is a promising strategy to fight cancer. Steinmann et al identified the eukaryotic initiation factor 4A1 (eIF4A1) as a prognostic factor in hepatocellular carcinoma (HCC), whose molecular function can be suppressed by treatment with inhibitors [7]. These eIF4A1 inhibitors led to high antiproliferative and strong pro-apoptotic effects in HCC, and the anticancer activities of the eIF4A1 inhibitors were significantly augmented by the combination with a pan-mTOR inhibitor.…”