Chemokine receptor CXCR4: An important player affecting the molecular-targeted drugs commonly used in hematological malignancies. Issue 12 (1st December 2020)

• Record Type: Journal Article
• Authors: Li, Liangliang; Chai, Ye; Wu, ChongYang; Zhao, Li
• Is Part Of: Expert review of hematology. Volume 13:Issue 12(2020)
• Page Start: 1387
• Page End: 1396
• Publication Date: 2020-12-01
• Subjects: Chemokine receptor CXCR4 -- CXCR4 antagonists -- molecular-targeted drugs -- resistance -- hematological malignancies; Hematology -- Periodicals; 616.15005
• DOI: 10.1080/17474086.2020.1839885
• Languages: English
• ISSNs: 1747-4086

Abstract

ABSTRACT: Introduction: 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). Areas covered: 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. Expert opinion: 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.