Yuri A. Piven¹, Danila V. Sorokin², Nastassia A. Varabyeva¹, Alexandra L. Mikhaylova², Fedor B. Bogdanov², Elena V. Shafranovskaya¹, Raman M. Puzanau³, Fedor A. Lakhvich¹, Alexander M. Scherbakov^2,4,*

Oncology Research, Vol.33, No.12, pp. 4049-4072, 2025, DOI:10.32604/or.2025.067832 - 27 November 2025

Abstract Background: The most aggressive forms of breast cancer are characterized by independence from steroid hormones but a strong dependence on growth factors. In such cancer cells, oncogenic receptors, including human epidermal growth factor receptor 2 (HER2), are activated, and their targeted inhibition represents an attractive therapeutic strategy. The study aimed to develop small-molecule potential dual heat shock protein 90 (HSP90)-HER2 inhibitors and evaluate them as anticancer agents in HER2-positive cells. Methods: The research project involved obtaining a series of compounds with potential dual inhibitory activity against HSP90 and HER2 by targeted organic synthesis, which was… More > Graphic Abstract

Jiahao Xue^1,#, Jingchang Zhang^2,#, Gang Chen³, Liucui Chen^4,*, Xinjun Lu^1,*

Oncology Research, Vol.33, No.9, pp. 2309-2329, 2025, DOI:10.32604/or.2025.063719 - 28 August 2025

Abstract Hepatocellular carcinoma (HCC) is a highly aggressive malignancy, largely driven by an immunosuppressive tumor microenvironment (TME) that facilitates tumor growth, immune escape, and resistance to therapy. Although immunotherapy—particularly immune checkpoint inhibitors (ICIs)—has transformed the therapeutic landscape by restoring T cell-mediated anti-tumor responses, their clinical benefit as monotherapy remains suboptimal. This limitation is primarily attributed to immunosuppressive components within the TME, including tumor-associated macrophages, regulatory T cells (Tregs), and myeloid-derived suppressor cells (MDSCs). To address these challenges, combination strategies have been explored, such as dual checkpoint blockade targeting programmed cell death protein 1 (PD-1), programmed death-ligand More >

Bi Feng^#, Siqi Yang^#, Zhiqiang He, Yushi Dai, Ruiqi Zou, Yafei Hu, Haijie Hu^*, Fuyu Li^*

Oncology Research, Vol.33, No.9, pp. 2353-2377, 2025, DOI:10.32604/or.2025.061422 - 28 August 2025

Abstract Objectives: Hepatocellular carcinoma (HCC) is among the most frequently occurring malignant tumors of the digestive tract and is associated with an increased mortality rate worldwide. This study aimed to develop and validate a prognostic model based on immunogenic cell death (ICD)-related genes to predict patient survival and guide individualized treatment strategies for HCC. Methods: ICD-related genes were identified from the GeneCards database using a relevance score threshold of >10. A combination of least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox analysis was used to screen prognostic genes and construct a risk score… More >

Gaofeng Pan^1,2,3, Jiali Li^1,2, Weijie Sun⁴, Jiayu He^1,2, Maoying Fu³, Yufeng Gao^1,2,*

Oncology Research, Vol.33, No.8, pp. 1991-2011, 2025, DOI:10.32604/or.2025.063993 - 18 July 2025

Abstract Aims: The aim of this study is to develop a prognostic model for hepatocellular carcinoma (HCC) using stemness-related genes (SRGs), while also pinpointing and validating pivotal genes associated with this process. Methods: Utilizing the TCGA and ICGC database, a prognostic stemness-related scores (SRS) for HCC through a combination of WGCNA and machine learning. Bioinformatics analysis evaluated tumor immune infiltration characteristics and drug sensitivity in different SRS subgroups, identifying the key gene TOMM40L. qRT-PCR and IHC were employed to detect the expression level of TOMM40 L. Kaplan-Meier survival analysis assessed the prognostic value of TOMM40L in… More >

Yanxi Peng¹, Honggen Yuan¹, Zhanjie Jiang², Xiaoqing Ou², Qian Zhang³, Kexin Yi¹, Yanbin Meng², Qun Xie^1,*

Oncology Research, Vol.33, No.7, pp. 1679-1693, 2025, DOI:10.32604/or.2025.062747 - 26 June 2025

Abstract Background: Expression of mRNA is widely regulated by N6-methyladenosine (m⁶A). An increasing number of studies have shown that m⁶A methylation, facilitated by methyltransferase 3 (METTL3), is crucial in the progression of tumors. Previous reports have indicated the involvement of both METTL3 and c-Src kinase in the evolution of liver cancer. However, the potential connection between c-Src and the METTL3-mediated mechanism in liver cancer progression remains elusive. Methods: The correlation expression between c-Src and METTL3 between liver cancer patients and the control group was analyzed using the TCGA database, and was further demonstrated by Western blot and… More >

DEXUE FAN^1,#, WEI SU^2,#, ZHAOWEN BI³, XINXING WANG¹, XIANWEN XU¹, MINGZE MA⁴, LICHAO ZHU⁵, ZHENHAI ZHANG^1,3,*, JUNLIN GAO^2,*

Oncology Research, Vol.33, No.6, pp. 1459-1472, 2025, DOI:10.32604/or.2025.060407 - 29 May 2025

Abstract Objectives: Apatinib has been reported to be a promising treatment for sorafenib-resistant hepatocellular carcinoma (HCC) patients. However, the underlying mechanism remains ambiguous. The study aimed to explore the efficacy of apatinib in sorafenib-resistant HCC and the underlying mechanism both in vitro and in vivo. Methods: After observing epithelial-mesenchymal transformation (EMT) changes in HepG2 and HepG2/Sorafenib cells, we treated them with varying concentrations of apatinib to assess its impact on sorafenib-resistant HCC. Subsequently, specific inhibitors of c-Jun N-terminal kinase (JNK, SP600125) and extracellular signal-regulated kinase (ERK, PD98059) were introduced to investigate whether apatinib influenced sorafenib-resistant HCC via modulation… More >

LIBO LIANG¹, XINYI WANG^2,3,4, YUPING ZENG^2,3,4, HAO CHEN^2,3,4, WEN ZHOU¹, HONGYING MU^2,3,4, GA LIAO^5,6,*

Oncology Research, Vol.33, No.6, pp. 1405-1421, 2025, DOI:10.32604/or.2024.056708 - 29 May 2025

Abstract Objectives: Exosomal long noncoding RNAs (lncRNAs) might facilitate epithelial–mesenchymal transition (EMT) in liver cancer after transarterial chemoembolization (TACE), thereby enhancing tumor cell invasiveness and migration. This study investigated the prognostic role of plasma exosomal long noncoding RNA-plasmacytoma variant translocation 1 (lncRNA-PVT1) in TACE treated hepatocellular carcinoma (HCC). Methods: Plasma exosomal lncRNA-PVT1 was evaluated via qPCR before and after TACE. Hepatoma cell behavior was investigated in different HCC cell lines. A lncRNA-PVT1 plasmid was synthesized and overexpressed, and si-lncRNA PVT1 was transfected into poorly invasive cells to reveal its influence on cell characteristics. The lncRNA-PVT1–FoxM1 interaction… More > Graphic Abstract

Ayda Baghery Saghchy Khorasani¹, Mahda Delshad², Mohammad-Javad Sanaei^2,3, Atieh Pourbagheri-Sigaroodi², Ali Pirsalehi⁴, Davood Bashash^2,*

BIOCELL, Vol.49, No.4, pp. 539-562, 2025, DOI:10.32604/biocell.2025.059970 - 30 April 2025

Abstract Hepatocellular carcinoma (HCC) is the most common primary liver tumor and the third leading cause of cancer-related mortality globally. The phosphatidylinositol-3 kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway is critically involved in HCC pathogenesis, stimulating uncontrolled cell proliferation, survival, and tumor progression. The overactivation of this pathway is strongly linked to poor prognosis, making it a crucial target for therapeutic intervention. The oncogenic roles of PI3K/AKT/mTOR components in HCC have been highlighted, noting that class I PI3K deregulation, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) upregulation, and mTOR overexpression could be associated… More >

BIAO WU^1,#, XIANLIN GUO^2,#, ZHISHI WU¹, LIANG CHEN^1,*, SUQING ZHANG^3,*

Oncology Research, Vol.33, No.4, pp. 975-988, 2025, DOI:10.32604/or.2025.058085 - 19 March 2025

Abstract Objectives: Although Yes-associated protein 1 (YAP1) is an important oncogene in hepatocellular carcinoma (HCC) progression, its nuclear localization prevents it from being considered a potential therapeutic target. Recently, studies have reported that coatomer protein complex subunit beta 2 (COPB2) also plays a critical role in HCC development; however its mechanism of action is unclear. This study aimed to investigate the role of COPB2 and YAP1 in the progression of HCC and to elucidate the underlying mechanisms. Methods: COPB2 and YAP1 expression in HCC tissues were first analyzed by database searches and immunohistochemistry. Nomogram and artificial… More >

DONG JIANG¹, ZHI QI³, ZHIYING XU^2,*, YIRAN LI^1,*

Oncology Research, Vol.33, No.3, pp. 709-722, 2025, DOI:10.32604/or.2024.050125 - 28 February 2025

Abstract Background: Hepatocellular carcinoma (HCC) is a prevalent liver malignancy. This study examined the roles of transforming growth factor beta (TGF-β) and cytochrome b5 domain containing 2 (CYB5D2) in HCC etiology and their prognostic biomarker potential. Methods: Key modules and prognostic genes were identified by analyzing the GSE101685 dataset by weighted gene co-expression network analysis (WGCNA) and Least absolute shrinkage and selection operator (LASSO) Cox regression. The expression levels of CYB5D2 and TGF-β in HCC cell lines were quantified using Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting (WB) assays. Effects of CYB5D2 overexpression on cell proliferation,… More >