Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL, USA.
Department of Radiology, College of Medicine, Michigan State University, East Lansing, MI, USA.
J Drug Target. 2022 Aug;30(7):687-708. doi: 10.1080/1061186X.2022.2055045. Epub 2022 Mar 31.
Breast cancer is considered as the second major cause of death among women with a high mortality rate worldwide. The exceptionally fast rate of metastasis, the emergence of drug-resistant mechanisms, and the occurrence of inadvertent side effects by cytotoxic chemotherapies often make conventional chemotherapy and immunotherapy treatments ineffective. Similar to other solid tumours, breast cancer can develop unique cellular and molecular characteristics forming an atypical permissive tumour microenvironment (TME). Due to the unique features of TME, cancer cells can further proliferate and coadapt with the stromal cells and evade immunosurveillance. Breast cancer cells aberrantly abundantly express various pieces of molecular machinery (the so-called oncomarkers) in favour of their survival, progression, metastasis, and further invasion. Such overexpressed oncomarkers can be exploited in the detection and targeted therapy of cancer. Among breast cancer oncomarkers, epidermal growth factor receptors, particularly HER2, are considered as clinically valid molecular targets not only for the thorough diagnosis but also for the targeted therapy of the disease using different conventional and advanced nanoscale treatment modalities. This review aims to elaborate on the recent advances in terms of targeted therapy of HER2-positive breast cancer, and discuss various types of multifunctional nanomedicines/theranostics, and antibody-/aptamer-drug conjugates.
乳腺癌被认为是全球女性死亡的第二大主要原因,死亡率很高。转移速度异常快、耐药机制的出现以及细胞毒性化疗药物的意外副作用的发生,常常使传统的化疗和免疫疗法治疗无效。与其他实体瘤类似,乳腺癌可以形成独特的细胞和分子特征,形成非典型的允许性肿瘤微环境(TME)。由于 TME 的独特特征,癌细胞可以进一步增殖,并与基质细胞共同适应,从而逃避免疫监视。乳腺癌细胞异常大量表达各种分子机制(所谓的致癌标志物),以有利于其存活、进展、转移和进一步侵袭。这些过表达的致癌标志物可用于癌症的检测和靶向治疗。在乳腺癌致癌标志物中,表皮生长因子受体,特别是 HER2,不仅被认为是彻底诊断的临床有效分子靶点,而且还被认为是使用不同的常规和先进纳米治疗模式对该疾病进行靶向治疗的临床有效分子靶点。本综述旨在阐述 HER2 阳性乳腺癌靶向治疗的最新进展,并讨论各种类型的多功能纳米药物/治疗药物和抗体/适体药物偶联物。