Laboratory of Experimental Oncology, IRCCS Istituto Ortopedico Rizzoli, Via di Barbiano 1/10, 40136 Bologna, Italy.
Department of Oncology, University of Torino, Via Santena 5/bis, 10126 Torino, Italy.
Cells. 2021 Sep 17;10(9):2461. doi: 10.3390/cells10092461.
The ATP-binding cassette (ABC) transporter superfamily consists of several proteins with a wide repertoire of functions. Under physiological conditions, ABC transporters are involved in cellular trafficking of hormones, lipids, ions, xenobiotics, and several other molecules, including a broad spectrum of chemical substrates and chemotherapeutic drugs. In cancers, ABC transporters have been intensely studied over the past decades, mostly for their involvement in the multidrug resistance (MDR) phenotype. This review provides an overview of ABC transporters, both related and unrelated to MDR, which have been studied in osteosarcoma and Ewing's sarcoma. Since different backbone drugs used in first-line or rescue chemotherapy for these two rare bone sarcomas are substrates of ABC transporters, this review particularly focused on studies that have provided findings that have been either translated to clinical practice or have indicated new candidate therapeutic targets; however, findings obtained from ABC transporters that were not directly involved in drug resistance were also discussed, in order to provide a more complete overview of the biological impacts of these molecules in osteosarcoma and Ewing's sarcoma. Finally, therapeutic strategies and agents aimed to circumvent ABC-mediated chemoresistance were discussed to provide future perspectives about possible treatment improvements of these neoplasms.
三磷酸腺苷结合盒（ABC）转运蛋白超家族由多种具有广泛功能的蛋白质组成。在生理条件下，ABC 转运蛋白参与激素、脂质、离子、外源性物质和其他多种分子的细胞内转运，包括广泛的化学底物和化疗药物。在过去几十年中，ABC 转运蛋白在癌症中受到了深入研究，主要是因为它们与多药耐药（MDR）表型有关。本综述概述了与 MDR 相关和不相关的 ABC 转运蛋白在骨肉瘤和尤文肉瘤中的研究情况。由于这两种罕见的骨肉瘤一线或挽救化疗中使用的不同骨干药物是 ABC 转运蛋白的底物，因此本综述特别关注了那些已经转化为临床实践或表明新的候选治疗靶点的研究；然而，也讨论了与药物耐药性不直接相关的 ABC 转运蛋白的研究结果，以便更全面地了解这些分子在骨肉瘤和尤文肉瘤中的生物学影响。最后，讨论了旨在规避 ABC 介导的化疗耐药性的治疗策略和药物，为这些肿瘤的可能治疗进展提供了未来的展望。
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