The First Clinical Medical College of Lanzhou University , Lanzhou, Gansu, China.
Department of Hematology, Lanzhou University Second Hospital , Lanzhou, Gansu, China.
Expert Rev Hematol. 2020 Dec;13(12):1387-1396. doi: 10.1080/17474086.2020.1839885. Epub 2020 Nov 10.
A variety of molecular-targeted drugs have been widely used in hematological malignancies and have shown great advances. Nevertheless, as the use of drugs in clinical practice increases, the problem of relapse or of the disease being refractory to treatment is becoming apparent. This problem is closely related to the C-X-C chemokine receptor 4 (CXCR4).
This review focuses mainly on the effect of CXCR4 on molecular-targeted drug resistance in hematological malignancies as well as the clinical efficacy of CXCR4 antagonists combined with molecular-targeted drugs. Relevant literatures published between 2006 and 2020 were searched using PubMed/Medline for this review.
Monoclonal antibodies and non-antibody molecular-targeted drugs provide new therapeutic approaches for B-lineage malignancies and leukemia, but the clinical activity of these drugs is affected by CXCR4. In general, high CXCR4 expression or mutation inhibits the effects of molecular-targeted drugs, but there are exceptions, and in studies of proteasome inhibitors bortezomib (Bz) in multiple myeloma (MM), low CXCR4 expression or loss of CXCR4 was associated with Bz resistance (BzR) and poor treatment outcomes. Given that CXCR4 is a critical mediator of molecular-targeted drug resistance, numerous studies have combined molecular-targeted drugs with CXCR4 antagonists, which synergistically enhance the anti-proliferative/pro-apoptotic effect of molecular-targeted drugs.
多种分子靶向药物已广泛应用于血液系统恶性肿瘤，并取得了很大进展。然而，随着临床实践中药物的应用增加，复发或疾病对治疗产生耐药的问题变得明显。这个问题与 C-X-C 趋化因子受体 4（CXCR4）密切相关。
本综述主要关注 CXCR4 对血液系统恶性肿瘤中分子靶向药物耐药性的影响，以及 CXCR4 拮抗剂与分子靶向药物联合的临床疗效。为了进行本综述，使用 PubMed/Medline 搜索了 2006 年至 2020 年期间发表的相关文献。
单克隆抗体和非抗体分子靶向药物为 B 细胞恶性肿瘤和白血病提供了新的治疗方法，但这些药物的临床疗效受到 CXCR4 的影响。一般来说，高 CXCR4 表达或突变会抑制分子靶向药物的作用，但也有例外，在多发性骨髓瘤（MM）中蛋白酶体抑制剂硼替佐米（Bz）的研究中，低 CXCR4 表达或 CXCR4 缺失与 Bz 耐药（BzR）和治疗结果不良相关。鉴于 CXCR4 是分子靶向药物耐药性的关键介导物，许多研究已经将分子靶向药物与 CXCR4 拮抗剂联合使用，这可以协同增强分子靶向药物的抗增殖/促凋亡作用。
