Instituto Estadual do Cérebro Paulo Niemeyer, Rio de Janeiro 20231-092, Brazil.
Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-901, Brazil.
Cancer Biol Med. 2020 May 15;17(2):253-269. doi: 10.20892/j.issn.2095-3941.2019.0284.
The ATP-binding cassette transporters (ABC transporters) have been intensely studied over the past 50 years for their involvement in the multidrug resistance (MDR) phenotype, especially in cancer. They are frequently overexpressed in both naive and post-treatment tumors, and hinder effective chemotherapy by reducing drug accumulation in cancer cells. In the last decade however, several studies have established that ABC transporters have additional, fundamental roles in tumor biology; there is strong evidence that these proteins are involved in transporting tumor-enhancing molecules and/or in protein-protein interactions that impact cancer aggressiveness, progression, and patient prognosis. This review highlights these studies in relation to some well-described cancer hallmarks, in an effort to re-emphasize the need for further investigation into the physiological functions of ABC transporters that are critical for tumor development. Unraveling these new roles offers an opportunity to define new strategies and targets for therapy, which would include endogenous substrates or signaling pathways that regulate these proteins.
过去 50 年来，ATP 结合盒转运蛋白（ABC 转运蛋白）因其与多药耐药（MDR）表型的关系而受到深入研究，尤其是在癌症方面。它们在初发和治疗后的肿瘤中经常过度表达，并通过减少癌细胞内药物积累来阻碍有效的化疗。然而，在过去十年中，多项研究已经证实 ABC 转运蛋白在肿瘤生物学中具有额外的基本作用；有强有力的证据表明，这些蛋白参与运输促进肿瘤的分子和/或影响癌症侵袭性、进展和患者预后的蛋白质-蛋白质相互作用。本综述重点介绍了这些与一些描述良好的癌症特征相关的研究，旨在再次强调需要进一步研究 ABC 转运蛋白的生理功能，这些功能对于肿瘤的发展至关重要。揭示这些新的作用为定义新的治疗策略和靶点提供了机会，这些策略和靶点可以包括调节这些蛋白的内源性底物或信号通路。
