Development, Maintenance, and Reversal of Multiple Drug Resistance: At the Crossroads of TFPI1, ABC Transporters, and HIF1.
Development, Maintenance, and Reversal of Multiple Drug Resistance: At the Crossroads of TFPI1, ABC Transporters, and HIF1.
复制标题
DOI：
10.3390/cancers7040877
复制
发表时间：
2015-10-16
期刊：
影响因子：
5.2
通讯作者：
Harkness T
中科院分区：
文献类型：
--
作者：
Arnason T;Harkness T
许多癌症的早期发现和改进的治疗方法正在提高生存率。尽管许多细胞毒性疗法被批准用于治疗侵袭性或转移性癌症；应答率很低，而且几乎普遍产生新的耐药性。几十年来；癌症的化疗包括阿霉素 (DOX) 等蒽环类药物；它在侵袭性肿瘤中的使用似乎仍然是一个可行的选择；但对 DOX 会产生耐药性；对于所有其他类别的化合物。我们最近的工作表明，抗凝血蛋白组织因子途径抑制剂 1α (TFPI1α) 在推动多重耐药性 (MDR) 的发展中发挥着重要作用；但不维修； MDR 状态。其他因素；例如ABC转运蛋白药物外排泵MDR-1/P-gp (ABCB1)和BCRP (ABCG2)； MDR 维护所需；以及发展。与治疗耐药性作斗争的患者群体特别需要新的治疗方案来使这些肿瘤细胞对治疗重新敏感。在这篇综述中，我们将 MDR 的发展、维持和逆转作为癌症生物学的三个不同阶段进行讨论。将探索利用这些阶段逆转 MDR 的可能方法。在临床失败之前对耐多药癌症进行早期分子检测有可能提供对抗耐多药癌症的新方法。
Early detection and improved therapies for many cancers are enhancing survival rates. Although many cytotoxic therapies are approved for aggressive or metastatic cancer; response rates are low and acquisition of de novo resistance is virtually universal. For decades; chemotherapeutic treatments for cancer have included anthracyclines such as Doxorubicin (DOX); and its use in aggressive tumors appears to remain a viable option; but drug resistance arises against DOX; as for all other classes of compounds. Our recent work suggests the anticoagulant protein Tissue Factor Pathway Inhibitor 1α (TFPI1α) plays a role in driving the development of multiple drug resistance (MDR); but not maintenance; of the MDR state. Other factors; such as the ABC transporter drug efflux pumps MDR-1/P-gp (ABCB1) and BCRP (ABCG2); are required for MDR maintenance; as well as development. The patient population struggling with therapeutic resistance specifically requires novel treatment options to resensitize these tumor cells to therapy. In this review we discuss the development, maintenance, and reversal of MDR as three distinct phases of cancer biology. Possible means to exploit these stages to reverse MDR will be explored. Early molecular detection of MDR cancers before clinical failure has the potential to offer new approaches to fighting MDR cancer.