Marin Jose J G, Monte Maria J, Macias Rocio I R, Romero Marta R, Herraez Elisa, Asensio Maitane, Ortiz-Rivero Sara, Cives-Losada Candela, Di Giacomo Silvia, Gonzalez-Gallego Javier, Mauriz Jose L, Efferth Thomas, Briz Oscar
Experimental Hepatology and Drug Targeting (HEVEPHARM) Group, University of Salamanca, IBSAL, 37007 Salamanca, Spain.
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Carlos III National Institute of Health, 28029 Madrid, Spain.
Cancers (Basel). 2022 Jul 20;14(14):3524. doi: 10.3390/cancers14143524.
Hepatobiliary, pancreatic, and gastrointestinal cancers account for 36% of the ten million deaths caused by cancer worldwide every year. The two main reasons for this high mortality are their late diagnosis and their high refractoriness to pharmacological treatments, regardless of whether these are based on classical chemotherapeutic agents, targeted drugs, or newer immunomodulators. Mechanisms of chemoresistance (MOC) defining the multidrug resistance (MDR) phenotype of each tumor depend on the synergic function of proteins encoded by more than one hundred genes classified into seven groups (MOC1-7). Among them, the efflux of active agents from cancer cells across the plasma membrane caused by members of the superfamily of ATP-binding cassette (ABC) proteins (MOC-1b) plays a crucial role in determining tumor MDR. Although seven families of human ABC proteins are known, only a few pumps (mainly MDR1, MRP1-6, and BCRP) have been associated with reducing drug content and hence inducing chemoresistance in hepatobiliary, pancreatic, and gastrointestinal cancer cells. The present descriptive review, which compiles the updated information on the expression of these ABC proteins, will be helpful because there is still some confusion on the actual relevance of these pumps in response to pharmacological regimens currently used in treating these cancers. Moreover, we aim to define the MOC pattern on a tumor-by-tumor basis, even in a dynamic way, because it can vary during tumor progression and in response to chemotherapy. This information is indispensable for developing novel strategies for sensitization.
每年全球因癌症导致的一千万人死亡中，肝胆、胰腺和胃肠道癌症占36%。造成这种高死亡率的两个主要原因是它们诊断较晚以及对药物治疗具有高度难治性，无论这些治疗是基于传统化疗药物、靶向药物还是新型免疫调节剂。定义每个肿瘤多药耐药（MDR）表型的化疗耐药机制（MOC）取决于一百多个分为七组（MOC1 - 7）的基因所编码蛋白质的协同功能。其中，由ATP结合盒（ABC）蛋白超家族成员导致活性药物从癌细胞跨质膜流出（MOC - 1b）在决定肿瘤MDR中起关键作用。虽然已知人类ABC蛋白有七个家族，但只有少数几种转运蛋白（主要是MDR1、MRP1 - 6和BCRP）与降低药物含量从而诱导肝胆、胰腺和胃肠道癌细胞的化疗耐药有关。本描述性综述汇编了这些ABC蛋白表达的最新信息，将有所帮助，因为对于这些转运蛋白在目前用于治疗这些癌症的药物治疗方案反应中的实际相关性仍存在一些困惑。此外，我们旨在逐个肿瘤地、甚至以动态方式定义MOC模式，因为它在肿瘤进展过程中以及对化疗的反应中可能会有所不同。这些信息对于开发新的增敏策略不可或缺。
