Méndez-Valdés Gabriel, Gómez-Hevia Francisca, Bragato Maria Chiara, Lillo-Moya José, Rojas-Solé Catalina, Saso Luciano, Rodrigo Ramón
Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago 8380000, Chile.
Department of Biomedical Sciences, Humanitas University, 20090 Milan, Italy.
Antioxidants (Basel). 2023 Feb 10;12(2):457. doi: 10.3390/antiox12020457.
Breast cancer is the most frequent malignant neoplastic disease in women, with an estimated 2.3 million cases in 2020 worldwide. Its treatment depends on characteristics of the patient and the tumor. In the latter, characteristics include cell type and morphology, anatomical location, and immunophenotype. Concerning this latter aspect, the overexpression of the HER2 receptor, expressed in 15-25% of tumors, is associated with greater aggressiveness and worse prognosis. In recent times some monoclonal antibodies have been developed in order to target HER2 receptor overexpression. Trastuzumab is part of the monoclonal antibodies used as targeted therapy against HER2 receptor, whose major problem is its cardiac safety profile, where it has been associated with cardiotoxicity. The appearance of cardiotoxicity is an indication to stop therapy. Although the pathophysiological mechanism is poorly known, evidence indicates that oxidative stress plays a fundamental role causing DNA damage, increased cytosolic and mitochondrial ROS production, changes in mitochondrial membrane potential, intracellular calcium dysregulation, and the consequent cell death through different pathways. The aim of this review was to explore the use of antioxidants as adjuvant therapy to trastuzumab to prevent its cardiac toxicity, thus leading to ameliorate its safety profile in its administration.
乳腺癌是女性中最常见的恶性肿瘤疾病,2020年全球估计有230万例病例。其治疗取决于患者和肿瘤的特征。对于肿瘤而言,特征包括细胞类型和形态、解剖位置以及免疫表型。关于后一个方面,在15% - 25%的肿瘤中表达的HER2受体的过表达与更高的侵袭性和更差的预后相关。近年来,为了靶向HER2受体过表达,已经开发了一些单克隆抗体。曲妥珠单抗是用作针对HER2受体的靶向治疗的单克隆抗体之一,其主要问题是心脏安全性,它与心脏毒性有关。心脏毒性的出现是停止治疗的指征。尽管病理生理机制尚不清楚,但有证据表明氧化应激起着关键作用,导致DNA损伤、胞质和线粒体活性氧生成增加、线粒体膜电位改变、细胞内钙失调,以及随后通过不同途径导致细胞死亡。本综述的目的是探讨使用抗氧化剂作为曲妥珠单抗的辅助治疗以预防其心脏毒性,从而改善其给药时的安全性。