Mylonakis Adam, Kozadinos Alexandros, Frountzas Maximos, Kapetanakis Emmanouil I, Lidoriki Irene, Despotidis Markos, Karanikki Eva, Triantafyllou Tania, Theodorou Dimitrios, Toutouzas Konstantinos G, Schizas Dimitrios
First Department of Surgery, Laikon General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece.
First Propaedeutic Department of Surgery, Hippocration General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece.
Cancers (Basel). 2025 Apr 21;17(8):1377. doi: 10.3390/cancers17081377.
Gastric and esophageal cancers are among the most lethal malignancies worldwide, necessitating improved biomarkers and therapeutic targets to improve patient outcomes. Visfatin, also known as nicotinamide phosphoribosyltransferase (NAMPT), is a metabolic enzyme and adipokine with emerging significance in cancer progression. It has been implicated in tumor cell proliferation, angiogenesis, immune modulation, and chemotherapy resistance, yet its clinical relevance in upper gastrointestinal (GI) cancers remains unclear. This review aims to explore visfatin's biochemical properties, its role in the pathogenesis of upper GI cancers, and its implications for potential therapeutic interventions. : A comprehensive review of the literature was conducted to evaluate the role of visfatin in gastric and esophageal cancer. We analyzed studies investigating visfatin expression in tumor tissues, blood, and adipose tissue, its prognostic significance, and its potential as a therapeutic target. Preclinical and clinical studies evaluating visfatin inhibitors were also reviewed. : Visfatin promotes tumor progression through the activation of key oncogenic pathways leading to increased angiogenesis, epithelial-mesenchymal transition (EMT), and immune suppression. Elevated visfatin levels are associated with advanced tumor stage, reduced response to chemotherapy, and poor prognosis in both gastric and esophageal cancers. Therapeutic agents targeting visfatin, such as the inhibitor FK866, have shown promising results in reducing tumor proliferation by >50%, improving chemoresistance, and restoring antitumor immunity in preclinical studies. However, clinical translation remains limited due to toxicity concerns and the need for more targeted therapies. : Visfatin is a promising biomarker and potential therapeutic target in gastric and esophageal cancer. However, its precise role and mechanisms require further investigation. The standardization of measurement techniques and large-scale clinical studies is needed to validate its prognostic and predictive value. Future research should focus on optimizing visfatin-targeted therapies, particularly in the context of obesity-associated malignancies and chemoresistant tumors.
胃癌和食管癌是全球最致命的恶性肿瘤之一，因此需要改进生物标志物和治疗靶点以改善患者预后。内脂素，也称为烟酰胺磷酸核糖转移酶（NAMPT），是一种代谢酶和脂肪因子，在癌症进展中具有越来越重要的意义。它与肿瘤细胞增殖、血管生成、免疫调节和化疗耐药有关，但其在上消化道（GI）癌症中的临床相关性仍不清楚。本综述旨在探讨内脂素的生化特性、其在上消化道癌症发病机制中的作用以及对潜在治疗干预的影响。：对文献进行了全面综述，以评估内脂素在胃癌和食管癌中的作用。我们分析了研究内脂素在肿瘤组织、血液和脂肪组织中的表达、其预后意义以及作为治疗靶点的潜力的研究。还综述了评估内脂素抑制剂的临床前和临床研究。：内脂素通过激活关键致癌途径促进肿瘤进展，导致血管生成增加、上皮-间质转化（EMT）和免疫抑制。内脂素水平升高与胃癌和食管癌的晚期肿瘤分期、化疗反应降低和预后不良有关。靶向内脂素的治疗药物，如抑制剂FK866，在临床前研究中显示出有前景的结果，可使肿瘤增殖减少>50%，改善化疗耐药性并恢复抗肿瘤免疫力。然而，由于毒性问题和对更有针对性治疗的需求，临床转化仍然有限。：内脂素是胃癌和食管癌中有前景的生物标志物和潜在治疗靶点。然而，其确切作用和机制需要进一步研究。需要测量技术的标准化和大规模临床研究来验证其预后和预测价值。未来的研究应专注于优化靶向内脂素的治疗，特别是在肥胖相关恶性肿瘤和化疗耐药肿瘤的背景下。
