Abraham Joseph, Salama Noha N, Azab Abdel Kareem
Cancer Biology Division, Department of Radiation Oncology, School of Medicine, Washington University in Saint Louis , St. Louis, MO , USA.
Leuk Lymphoma. 2015 Jan;56(1):26-33. doi: 10.3109/10428194.2014.907890. Epub 2014 Jun 5.
Multiple myeloma (MM) is a malignant neoplastic cancer of the plasma cells that involves the bone marrow. The majority of patients with MM initially respond to chemotherapy, but they eventually become resistant to later drug therapy. One of the reasons for drug resistance in patients with MM is efflux transporters. P-glycoprotein (P-gp) is the most studied of the multidrug resistance proteins, and is up-regulated in response to many chemotherapeutic drugs. This up-regulation of P-gp causes a decrease in the intracellular accumulation of these drugs, limiting their therapeutic efficacy. In this review, we focus on the role of P-gp in drugs used for patients with MM. P-gp has been found to be an important factor with regard to drug resistance in many of the drug classes used in the treatment of MM (proteasome inhibitors, anthracyclines, alkylating agents and immunomodulators are examples). Thus, our further understanding of its mechanism and inhibitory effects will help us decrease drug resistance in patients with MM.
多发性骨髓瘤(MM)是一种累及骨髓的浆细胞恶性肿瘤性癌症。大多数MM患者最初对化疗有反应,但最终会对后续的药物治疗产生耐药性。MM患者产生耐药性的原因之一是外排转运蛋白。P-糖蛋白(P-gp)是研究最多的多药耐药蛋白,在许多化疗药物的作用下会上调。P-gp的这种上调导致这些药物在细胞内的积累减少,限制了它们的治疗效果。在本综述中,我们重点关注P-gp在MM患者所用药物中的作用。已发现P-gp是MM治疗中使用的许多药物类别(蛋白酶体抑制剂、蒽环类药物、烷化剂和免疫调节剂为例)耐药性方面的一个重要因素。因此,我们对其机制和抑制作用的进一步了解将有助于我们降低MM患者的耐药性。