Guoliang Zhong¹, Tianqing Yang¹, Shuqi Lin¹, Muyi Zhong^1,2,*

Oncology Research, Vol.34, No.6, 2026, DOI:10.32604/or.2026.076300 - 21 May 2026

Abstract Hormone Receptor-positive/Human Epidermal Growth Factor Receptor 2-negative (HR+/HER2−) breast cancer treatment has made a breakthrough due to the introduction of cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors. This article mainly reviews the mechanisms of action, clinical efficacy, and current application status of CDK4/6 inhibitors, including Palbociclib, Ribociclib, Abemaciclib, and the emerging Dalpiciclib. The advantages and limitations of different treatment stages are also discussed. CDK4/6 inhibitors have excellent efficacy in prolonging progression-free survival (PFS) and overall survival (OS), and have become a key option for HR+/HER2− breast cancer first-line and adjuvant treatment. The issues of drug More >

Pietro Tralongo^1,#,*, Mariagiovanna Ballato^1,#, Valeria Zuccalà², Vincenzo Fiorentino², Walter Giordano¹, Giovanna Casili³, Fabiola Bellinghieri⁴, Gerardo Caruso⁵, Filippo Flavio Angileri⁵, Guido Fadda², Maurizio Martini^2,§, Maria Caffo^5,§

Oncology Research, Vol.34, No.6, 2026, DOI:10.32604/or.2026.076088 - 21 May 2026

Abstract Glioblastoma (GB) is the most common primary malignant brain tumor of adulthood, and despite optimal safe resection and chemoradiation, it is still lethal. Neuroscience of cancer has shown that neuronal activities, as well as neurotransmitters, play an active role in the glioma microenvironment. This article aims to integrate the existing literature on the role of neurotransmitters and their receptors in glioblastoma, as well as other gliomas, highlighting areas of therapeutic intervention in the neuron-tumor interface. We will describe the neuro–glioma interface, including functional neuron–glioma synapses and activity-dependent tumor growth. We will also discuss major neurotransmitter… More > Graphic Abstract

Cristina Díaz del Arco^1,2,*, Luis Ortega Medina^1,2, Patricia Barreiro Sanabria², Andrés Sánchez Pernaute³, Lourdes Estrada Muñoz⁴, Elena Molina Roldán⁵, María Jesús Fernández Aceñero^1,2

Oncology Research, Vol.34, No.6, 2026, DOI:10.32604/or.2026.075609 - 21 May 2026

Abstract Background: Claudin 18.2 (CLDN18.2) has become a clinically relevant therapeutic target in gastric adenocarcinoma (GC), with zolbetuximab now approved for use in CLDN18.2-positive, HER2-negative advanced disease. The aim of this study was to evaluate the prevalence, intratumoral reproducibility, and clinicopathologic associations of CLDN18.2 expression in a Western cohort of resected GC. Methods: CLDN18.2 expression was evaluated by immunohistochemistry in 204 resected GCs arranged in tissue microarrays containing duplicate tumor cores corresponding to the tumor center and invasive front. Correlations between paired cores, clinicopathologic parameters, additional biomarkers (E-cadherin, HER2, p53, mismatch repair (MMR)), and clinical outcomes were… More >

Evangelia Pantazaka^1,#, Dimitrios Papakonstantinou^1,#, Argyro Roumeliotou¹, Dafni Graikioti², Sotirios Tsakas¹, Nefeli Zacharopoulou³, Stuart S. Martin⁴, Athanasios Kotsakis⁵, Constantinos M. Athanassopoulos², Catherine Alix-Panabières^6,7,8, Galatea Kallergi^1,*

Oncology Research, Vol.34, No.6, 2026, DOI:10.32604/or.2026.075600 - 21 May 2026

Abstract Objectives: Circulating tumor cells (CTCs) drive metastasis and exhibit resistance to conventional therapies, making them crucial therapeutic targets. Artesunate (AS), a derivative of artemisinin, displays anticancer activity, including inhibition of JunB proto-oncogene (JUNB) and programmed death ligand-1 (PD-L1) and upregulation of Vimentin (VIM), markers related to poor prognosis in CTCs. This study aimed to evaluate the effects of AS on adherent and non-adherent cancer cell lines (breast, lung, colon), the patient-derived colon cancer CTC-MCC-41 line, and CTCs from small-cell lung cancer (SCLC) patients. Methods: AS’s effect was evaluated using TetherChip technology. Cell viability was measured using… More > Graphic Abstract

Thanh Hoa Vo^1,2, Edel McNeela^1,2, Orla O’Donnovan^1,2, Jai Prakash Mehta³, Van Hoa Nguyen⁴, Sweta Rani^1,2,*

Oncology Research, Vol.34, No.6, 2026, DOI:10.32604/or.2026.075346 - 21 May 2026

Abstract Long non-coding RNAs (lncRNAs) have emerged as key regulators of drug resistance in human epidermal growth factor receptor 2 (HER2)-positive breast cancer, a subtype in which both intrinsic and acquired resistance to HER2-targeted therapies remain major clinical challenges. Although mechanistic studies have begun to reveal how lncRNAs modulate signaling pathways, interact with microRNAs, and influence the tumor microenvironment, dedicated investigations in HER2-positive disease are still limited. This review synthesizes current evidence across epigenetic, transcriptional, and post-transcriptional mechanisms of resistance, including competing endogenous RNA (ceRNA) networks, RNA-binding protein interactions, and exosome-mediated intercellular communication. Particular emphasis is… More >

Kaidi Yin, Lili Deng, Wen Liu^*

Oncology Research, Vol.34, No.6, 2026, DOI:10.32604/or.2026.075185 - 21 May 2026

Abstract Objectives: Although claudin-1 (CLDN1) interacts with Cluster of Differentiation 81 (CD81) in various cell types, the specific mechanism underlying this interaction and its functional implications in colorectal cancer (CRC) cells remain poorly understood. This study outlines the regulatory role of CLDN1 in CRC cell tumorigenicity through its interaction with CD81, elucidating the underlying signaling cascade. Methods: Changes in the expression of CLDN1 and CD81, as well as their correlation with the survival of CRC patients, were analyzed using samples from The Cancer Genome Atlas database, the Kaplan‒Meier plotter database, and tissue microarrays. CLDN1 and CD81 were… More >

Mariana Lopes^1,#, Carlos Vila Nova^2,3,#, Rui Caetano Oliveira^3,4, Fernando Schmitt⁵, Fernando Mendes^1,6,7,8,9,*, Diana Martins^1,6,7,8

Oncology Research, Vol.34, No.6, 2026, DOI:10.32604/or.2026.074215 - 21 May 2026

Abstract Objectives: Triple-negative breast cancer (TNBC) accounts for approximately 15% of all invasive breast cancers and is characterized by aggressive behavior, limited therapeutic options, and poor clinical outcomes. Due to the absence of hormone receptors and HER2 expression, systemic treatment relies predominantly on chemotherapy, which is associated with high rates of early recurrence and mortality. Emerging evidence suggests that alterations in the microbiome can contribute to TNBC progression and influence therapeutic response, particularly affecting the efficacy of chemotherapy and immunotherapy through immune-mediated mechanisms; however, its role in TNBC remains incompletely understood. This systematic review aims to explore… More >

Yi-Sian Huang^1,2, Chung-Yung Ma^1,2, Hsiao-Yuh Roan³, Cheng-Hsiung Chiang⁴, Hsiao-Hui Tsou⁴, Chen-Hui Chen³, Yi-Fan Lin², Horng-Dar Wang², Chiou-Hwa Yuh^1,5,6,7,*

Oncology Research, Vol.34, No.6, 2026, DOI:10.32604/or.2026.074145 - 21 May 2026

Abstract Objectives: Hepatocellular carcinoma (HCC) arising in metabolic dysfunction–associated steatotic liver disease (MASLD) develops under lipid-rich stress and inflammatory remodeling, which can alter therapeutic windows. We aimed to determine whether phenotypic response surface–guided optimization (PRS-OPT) can nominate hepatocyte-sparing propolis–metformin–regorafenib (PMR) dose windows that retain antitumor activity under MASLD-like fatty-acid (FA) stress and translate to an in vivo immune endpoint. Methods: PMR combinations were profiled in hepatoma cell lines (PLC/PRF/5 and HepG2) and non-malignant hepatocytes (THLE-2) under FA-free and FA-enriched conditions. Quadratic response surfaces were fitted and used for constrained dose nomination, followed by in vitro validation. Cell-death contributions were… More >

Wenjian Zeng¹, Xianglong Li², Hao Cai¹, Qingyu Zhou², Shuangshuang Sun², Pingping Li², Sunlong Li¹, Zhi Chen^2,*

Oncology Research, Vol.34, No.6, 2026, DOI:10.32604/or.2026.073934 - 21 May 2026

Abstract Objectives: Cisplatin resistance is a major obstacle in the treatment of renal cell carcinoma (RCC), severely compromising therapeutic efficacy and patient prognosis. This study aimed to clarify the role and molecular mechanism of cyclin-dependent kinase 4 (CDK4) in cisplatin resistance of RCC. Methods: Immunohistochemistry (IHC) was used to detect the expression of CDK4 in cisplatin-resistant RCC tissues. In RCC cells and their drug-resistant sublines, CDK4 overexpression/knockdown assays were performed to evaluate the effects on cisplatin resistance and malignant progression. An in vivo model was established, to verify the in vivo function of CDK4. Transcriptome sequencing (RNA-seq), Cleavage Under… More >

Ji Hoon Jang, Joo-Young Kim, Tae-Jin Lee^*

Oncology Research, Vol.34, No.6, 2026, DOI:10.32604/or.2026.073660 - 21 May 2026

Abstract Molecular glue degraders (MGDs) are an emerging class of small molecules that promote selective protein degradation by inducing neomorphic interactions between E3 ubiquitin ligases and non-native substrates, referred to as neosubstrates. Clinically validated examples include thalidomide analogs that recruit cereblon (CRBN) to degrade IKAROS family zinc finger 1/3 in multiple myeloma, and arylsulfonamide-based MGDs that promote the degradation of RNA-binding protein 39 in acute myeloid leukemia and solid tumors. These molecules highlight the therapeutic potential of this modality in oncology. These findings underscore the promise of MGDs for eliminating oncogenic proteins previously considered undruggable and… More > Graphic Abstract