Mechanisms of tyrosine kinase inhibitor resistance in renal cell carcinoma  

作　　者：Patrick L.Sweeney Yash Suri Arnab Basu Vadim S.Koshkin Arpita Desai 

机构地区：[1]Deming Department of Medicine,Tulane University School of Medicine,New Orleans,LA 70112,USA [2]University of Arizona College of Medicine,Tucson,AZ 85724,USA [3]Division of Hematology and Oncology,Department of Medicine,University of Alabama at Birmingham Heersink School of Medicine,Birmingham,AL35233,USA [4]Division of Hematology and Oncology,Department of Medicine,University of California at San Francisco School of Medicine,SanFrancisco,CA94143,USA

出　　处：《Cancer Drug Resistance》2023年第4期858-873,共16页癌症耐药（英文）

摘　　要：Renal cell carcinoma(RCC),the most prevalent type of kidney cancer,is a significant cause of cancer morbidity and mortality worldwide.Antiangiogenic tyrosine kinase inhibitors(TKls),in combination with immune checkpoint inhibitors(ICls),are among the first-line treatment options for patients with advanced RCC.These therapies target the vascular endothelial growth factor receptor(VEGFR)tyrosine kinase pathway and other kinases crucial to cancer proliferation,survival,and metastasis.TKls have yielded substantial improvements in progression-free survival(PFS)and overall survival(OS)for patients with advanced RCC.However,nearly all patients eventually progress on these drugs as resistance develops.This review provides an overview of TKl resistance in RCC and explores different mechanisms of resistance,including upregulation of alternative proangiogenic pathways,epithelial-mesenchymal transition(EMT),decreased intracellular drug concentrations due to efflux pumps and lysosomal sequestration,alterations in the tumor microenvironment including bone marrow-derived cells(BMDCs)and tumor-associated fibroblasts(TAFs),and genetic factors such as single nucleotide polymorphisms(SNPs).A comprehensive understanding of these mechanisms opens the door to the development of innovative therapeutic approaches that can effectively overcome TKl resistance,thereby improving outcomes for patients with advanced RCC.

关 键 词：Antiangiogenic tyrosine kinase inhibitors renal cell carcinoma acquired resistance SUNITINIB tumor microenvironment immune checkpoint inhibitors 

分 类 号：R737.11[医药卫生—肿瘤]