Colony-stimulating factor-1 receptor inhibition combined with paclitaxel exerts effective antitumor effects in the treatment of ovarian cancer  

作　　者：Meijia Yu Yiming Wu Qingfang Li Weiqi Hong Yang Yang Xiaoyi Hu Yanfei Yang Tianqi Lu Xia Zhao Xiawei Wei 

机构地区：[1]Laboratory of Aging Research and Cancer Drug Target,State Key Laboratory of Biotherapy and Cancer Center,National Clinical Research Center for Geriatrics,West China Hospital,Sichuan University,Chengdu,Sichuan 610041,China [2]Department of Gynecology and Obstetrics,Development and Related Disease of Women and Children Key Laboratory of Sichuan Province,Key Laboratory of Birth Defects and Related Diseases of Women and Children,Ministry of Education,West China Second Hospital,Sichuan University,Chengdu,Sichuan 610041,China [3]Department of Obstetrics and Gynecology,The First Affiliated Hospital,Army Medical University,Chongqing 400038,China

出　　处：《Genes & Diseases》2024年第3期400-416,共17页基因与疾病（英文）

基　　金：supported by the National Science Foundation for Excellent Young Scholars(China)(No.32122052);the National Natural Science Foundation Regional Innovation and Development(China)(No.U19A2003).

摘　　要：Ovarian cancer is the tumor with the highest mortality among gynecological malig-nancies.Studies have confirmed that paclitaxel chemoresistance is associated with increased infiltration of tumor-associated macrophages(TAMs)in the microenvironment.Colony-stimu-lating factor 1(CSF-1)receptor(CSF-1R)plays a key role in regulating the number and differ-entiation of macrophages in certain solid tumors.There are few reports on the effects of targeted inhibition of CSF-1R in combination with chemotherapy on ovarian cancer and the tu-mor microenvironment.Here,we explored the antitumor efficacy and possible mechanisms of the CSF-1R inhibitor pexidartinib(PLX3397)when combined with the first-line chemothera-peutic agent paclitaxel in the treatment of ovarian cancer.We found that CSF-1R is highly ex-pressed in ovarian cancer cells and correlates with poor prognosis.Treatment by PLX3397 in combination with paclitaxel significantly inhibited the growth of ovarian cancer both in vitro and in vivo.Blockade of CSF-1R altered the macrophage phenotype and reprogrammed the immunosuppressive cell population in the tumor microenvironment.

关 键 词：CSF-1R OVARIANCANCER PACLITAXEL PLX3397 Targeted therapy Tumor-associated macrophages 

分 类 号：R737.31[医药卫生—肿瘤]