TAK-901, a novel EPHA2 inhibitor as a therapeutic strategy against prostate cancerLiu, Fu, Wu
et alCell Signal (2025) 131, 111750
Abstract: Prostate cancer is the most common cancer and remains a leading cause of cancer-related deaths among men worldwide. Androgen deprivation therapy continues to be the cornerstone of treatment for prostate cancer. However, the efficacy of this treatments is often limited, leading to the emergence of drug resistance and tumor recurrence. TAK-901, an inhibitor of Aurora kinase B, has been shown to inhibit tumor growth both in vitro and in vivo models. To date, the effect of TAK-901 on prostate cancer and the underlying mechanism remain unknown. In this study, we found that TAK-901 could inhibit proliferation, colony formation and migration, while also inducing apoptosis in prostate cancer cells. We further demonstrated that TAK-901 activates the CHK1 signaling pathway, leading to G2/M-phase arrest in these cells. Additionally, we identified EPHA2 as a novel therapeutic target of TAK-901. By mutating the binding sites between EPHA2 and TAK-901, we discovered that these mutations could reverse the anti-proliferative effects of TAK-901 in prostate cancer models. Our study is the first to reveal that TAK-901 induces apoptosis in prostate cancer cells and inhibits cell growth by targeting EPHA2. These findings provide valuable insights into the underlying mechanisms of TAK-901 and may develop its therapeutic applications in prostate cancer.Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.
Broad-spectrum antiviral activity of Ganoderma microsporum immunomodulatory protein: Targeting glycoprotein gB to inhibit EBV and HSV-1 infections via viral fusion blockageVo, Ho, Wu
et alInt J Biol Macromol (2025) 307 (Pt 3), 142179
Abstract: Epstein-Barr virus (EBV) and herpes simplex virus-1 (HSV-1) are members of the Herpesviridae family and cause various human malignancies and acute infections. Despite their clinical significance, effective treatments remain limited. Here, we report the broad-spectrum antiviral activity of Ganoderma microsporum immunomodulatory protein (GMI), a safe dietary ingredient known for its immunomodulatory, anti-tumor, and antiviral properties. GMI effectively blocks EBV infection in epithelial cells in a dose-dependent manner by targeting both viral and host cells. Notably, GMI displays antiviral activity across multiple EBV strains in epithelial cell infection and represses EBV infection in primary B cells. Mechanistically, GMI interacts with the EBV fusion glycoprotein gB and the host epithelial receptor EphA2 to disrupt viral fusion. Given the structural conservation of gB among herpesviruses, GMI was tested against HSV-1. Remarkably, GMI effectively blocks HSV-1 infection by targeting viral binding and fusion, as well as interacting with HSV-1 gB. In silico modeling suggests that GMI may interact with EBV and HSV-1 gB domain I, contributing to its antiviral activity. Our findings provide the first evidence that GMI suppresses both EBV and HSV-1 infections by targeting the conserved gB-mediated fusion process, suggesting its potential as an antiviral against herpesviruses that rely on fusion-mediated entry.Copyright © 2025. Published by Elsevier B.V.
Comprehensive clinical and genetic characterization of hyperprogressive biliary tract cancer during PD-1 blockade monotherapy: case report and literature reviewWang, Yang, Guo
et alBMC Med Genomics (2025) 18 (1), 52
Abstract: Some genetically characterized patients show the rapid disease progression during immune checkpoint inhibitors (ICIs) monotherapy, a phenomenon known as hyperprogressive disease (HPD).Herein we report a relevant case of biliary tract cancer (BTC) that initially responded to gemcitabine plus oxaliplatin (GEMOX) and PD-1 blockade but subsequently developed HPD in the process of PD-1 blockade maintenance therapy, leading to death within two weeks. Genomic analysis revealed mutations in CDKN2A, PIK3CA, KRAS and EPHA2 in both baseline and hyperprogressive plasma and tumor samples. Notably, higher KRAS mutation abundance was observed in plasma and ascites after disease progression.These findings suggest a potential association between these negative genes especially KRAS mutation and HPD. Therefore, administration of PD-1 blockade monotherapy in this subgroup of patients harboring KRAS mutation should be performed with caution. Further studies are warranted to confirm these results and explore the correlation between genomic mutations and HPD.© 2025. The Author(s).
miR-1297 is frequently downmodulated in flat epithelial atypia of the breast and promotes mammary neoplastic transformation via EphrinA2 regulationScafetta, Rampioni Vinciguerra, Giglio
et alJ Exp Clin Cancer Res (2025) 44 (1), 96
Abstract: Breast cancer ranks as the most prevalent form of cancer globally. Currently, advanced screening methods have significantly improved early detection rates. These achievements have led to more non-invasive cancer diagnoses and underscored the clinical relevance of precursor lesions like flat epithelial atypia (FEA), a histological condition characterized by mild atypical changes in the normal epithelium lining the mammary ducts. Despite the increasing detection of FEA in mammary biopsy, our understanding of the biological behavior of this entity remains limited and, as a consequence, the clinical management of patients is still being debated. Evidence from the literature indicates that dysregulation of microRNAs contributes to all stages of breast cancer progression, potentially serving as valuable markers of disease evolution. In this study, through a comparison of the microRNA profiles of normal mammary epithelium, FEA, and non-invasive breast cancer in three cohorts of patients, we identified downregulation of miR-1297 as a common feature in both FEA and non-invasive breast cancer compared to the normal counterpart. Mechanistically, overexpression of miR-1297 inhibits the growth of breast cancer cells by targeting the oncogenic receptor tyrosine kinase EphrinA2. In contrast, downregulation of miR-1297 increases proliferation and alters the morphology of normal mammary epithelial cells in a three-dimensional context. These findings pinpoint the downregulation of miR-1297 as an early event in mammary transformation and suggest its potential role as a driver of progression in FEA, harboring the capacity to evolve into malignancy.© 2025. The Author(s).
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