Gómez Benito Blanco, Casas-Nebra Francisco Javier, Pérez-Fentes Daniel, Bravo Susana B, Rodríguez-Silva Laura, Núñez Cristina
Urology Division, Lucus Augusti University Hospital (HULA), Servizo Galego de Saúde (SERGAS), 27002 Lugo, Spain.
Urology Division, University Clinical Hospital of Santiago de Compostela (CHUS), Servizo Galego de Saúde (SERGAS), 15706 Santiago de Compostela, Spain.
Int J Mol Sci. 2025 Aug 1;26(15):7413. doi: 10.3390/ijms26157413.
Mitomycin C (MMC) is a widely employed chemotherapeutic agent, particularly in non-muscle invasive bladder cancer (NMIBC), where it functions by inducing DNA cross-linking and promoting tumor cell apoptosis. However, the tumor microenvironment (TME) significantly influences the therapeutic efficacy of MMC. Among the key regulators within the TME, the complement system and the coagulation pathway play a crucial role in modulating immune responses to cancer therapies, including MMC. This article explores the interaction between platinum nanoparticles (PtNPs) with human serum (HS) of NMIBC patients (T1 and Ta subtypes) at three different points: before the chemotherapy instillation of MMC () and three () and six months () after the treatment with MMC. This novel nanoproteomic strategy allowed the identification of a TME proteomic signature associated with the response to MMC treatment. Importantly, two proteins involved in the immune response were found to be deregulated across all patients (T1 and Ta subtypes) during MMC treatment: prothrombin (F2) downregulated and complement component C7 (C7) upregulated. By understanding how these biomarker proteins interact with MMC treatment, novel therapeutic strategies can be developed to enhance treatment outcomes and overcome resistance in NMIBC.
丝裂霉素C（MMC）是一种广泛应用的化疗药物，尤其在非肌层浸润性膀胱癌（NMIBC）中，它通过诱导DNA交联和促进肿瘤细胞凋亡发挥作用。然而，肿瘤微环境（TME）显著影响MMC的治疗效果。在TME的关键调节因子中，补体系统和凝血途径在调节对包括MMC在内的癌症治疗的免疫反应中起着关键作用。本文探讨了铂纳米颗粒（PtNPs）与NMIBC患者（T1和Ta亚型）的人血清（HS）在三个不同时间点的相互作用：MMC化疗灌注前（）以及MMC治疗后三个月（）和六个月（）。这种新颖的纳米蛋白质组学策略能够识别与MMC治疗反应相关的TME蛋白质组特征。重要的是，在MMC治疗期间，发现所有患者（T1和Ta亚型）中涉及免疫反应的两种蛋白质失调：凝血酶原（F2）下调，补体成分C7（C7）上调。通过了解这些生物标志物蛋白质如何与MMC治疗相互作用，可以开发新的治疗策略来提高治疗效果并克服NMIBC中的耐药性。
