Bucci-Muñoz María, Gola Aldana Magalí, Rigalli Juan Pablo, Ceballos María Paula, Ruiz María Laura
Facultad de Ciencias Bioquímicas y Farmacéuticas (UNR), Instituto de Fisiología Experimental (CONICET), Rosario 2000, Argentina.
Department of Clinical Pharmacology and Pharmacoepidemiology, Heidelberg University Hospital, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.
Life (Basel). 2023 Jul 27;13(8):1633. doi: 10.3390/life13081633.
Cancer multidrug resistance (MDR) is one of the main mechanisms contributing to therapy failure and mortality. Overexpression of drug transporters of the ABC family (ATP-binding cassette) is a major cause of MDR. Extracellular vesicles (EVs) are nanoparticles released by most cells of the organism involved in cell-cell communication. Their cargo mainly comprises, proteins, nucleic acids, and lipids, which are transferred from a donor cell to a target cell and lead to phenotypical changes. In this article, we review the scientific evidence addressing the regulation of ABC transporters by EV-mediated cell-cell communication. MDR transfer from drug-resistant to drug-sensitive cells has been identified in several tumor entities. This was attributed, in some cases, to the direct shuttle of transporter molecules or its coding mRNA between cells. Also, EV-mediated transport of regulatory proteins (e.g., transcription factors) and noncoding RNAs have been indicated to induce MDR. Conversely, the transfer of a drug-sensitive phenotype via EVs has also been reported. Additionally, interactions between non-tumor cells and the tumor cells with an impact on MDR are presented. Finally, we highlight uninvestigated aspects and possible approaches to exploiting this knowledge toward the identification of druggable processes and molecules and, ultimately, the development of novel therapeutic strategies.
癌症多药耐药性（MDR）是导致治疗失败和死亡的主要机制之一。ABC家族（ATP结合盒）药物转运蛋白的过表达是MDR的主要原因。细胞外囊泡（EVs）是机体大多数细胞释放的参与细胞间通讯的纳米颗粒。其货物主要包括蛋白质、核酸和脂质，它们从供体细胞转移到靶细胞并导致表型变化。在本文中，我们综述了关于EV介导的细胞间通讯对ABC转运蛋白调控的科学证据。在多个肿瘤实体中已发现多药耐药性从耐药细胞转移到敏感细胞。在某些情况下，这归因于转运蛋白分子或其编码mRNA在细胞间的直接穿梭。此外，有研究表明EV介导的调节蛋白（如转录因子）和非编码RNA的转运可诱导多药耐药性。相反，也有报道称通过EVs可转移药物敏感表型。此外，还介绍了非肿瘤细胞与肿瘤细胞之间对多药耐药性有影响的相互作用。最后，我们强调了尚未研究的方面以及利用这些知识来识别可成药过程和分子并最终开发新治疗策略的可能方法。
