Anti-lymphangiogenesis for boosting drug accumulation in tumors
作者机构：CAS Key Laboratory for Biomedical Effects of Nanomaterials&NanosafetyCAS Center for Excellence in NanoscienceNational Center for Nanoscience and TechnologyBeijing 100190China Sino-Danish CollegeUniversity of Chinese Academy of SciencesBeijing 100190China Sino-Danish Center for Education and ResearchBeijing 100190China Department of BioengineeringUniversity of PennsylvaniaPhiladelphiaPA 19104USA School of Nanoscience and EngineeringUniversity of Chinese Academy of SciencesBeijing 100049China
出 版 物：《Signal Transduction and Targeted Therapy》 (信号转导与靶向治疗（英文）)
年 卷 期：2024年第9卷第5期
页 面：2161-2175页
核心收录：
学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学]
基 金：This work was supported by grants from the National Key Research and Development Program of China(2022YFA1206800,2021YFA1201103) the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB36000000,G.N.) the National Natural Science Foundation of China(32371520) the Beijing Natural Science Foundation(Z210017) the Key Research Program of Frontier Sciences CAS(ZDBS-LY-SLH039),the Youth Innovation Promotion Association CAS(2022166) the Fundamental Research Funds for the Central Universities.The authors thank Han Ouyang(School of Nanoscience and Engineering,University of Chinese Academy of Sciences)for the help of intratumoral interstitial fluid pressure(IFP)assay
主 题：drugs angiogenesis metastasis
摘 要：The inadequate tumor accumulation of anti-cancer agents is a major shortcoming of current therapeutic drugs and remains an even more significant concern in the clinical prospects for *** strategies aiming at regulating the intratumoral permeability of therapeutic drugs have been explored in preclinical studies,with a primary focus on vascular regulation and stromal ***,these methods may trigger or facilitate tumor metastasis as a ***,there is an urgent need for innovative strategies that boost intratumoral drug accumulation without compromising treatment *** another important factor affecting drug tumor accumulation besides vasculature and stroma,the impact of tumor-associated lymphatic vessels(LVs)has not been widely *** the current research,we verified that anlotinib,a tyrosine kinase inhibitor with anti-lymphangiogenesis activity,and SAR131675,a selective VEGFR-3 inhibitor,effectively decreased the density of tumor lymphatic vessels in mouse cancer models,further enhancing drug accumulation in tumor *** combining anlotinib with therapeutic drugs,including doxorubicin(Dox),liposomal doxorubicin(Lip-Dox),and anti-PD-L1 antibody,we observed improved anti-tumor efficacy in comparison with monotherapy ***,this strategy significantly reduced tumor metastasis and elicited stronger anti-tumor immune *** work describes a new,clinically transferrable approach to augmenting intratumoral drug accumulation,which shows great potential to address the current,unsatisfactory efficacies of therapeutic drugs without introducing metastatic risk.
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