Colony-stimulating factor-1 receptor inhibition combined with paclitaxel exerts effective antitumor effects in the treatment of ovarian cancer
Ovarian cancer is the tumor with the highest mortality among gynecological malignancies. Studies have confirmed that paclitaxel chemoresistance is associated with increased infiltration of tumor-associated macrophages (TAMs) in the microenvironment. Colony-stimulating factor 1 (CSF-1) receptor (CSF-...
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| Format: | Article |
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KeAi Communications Co., Ltd.
2024-05-01
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| Series: | Genes and Diseases |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352304223002349 |
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| author | Meijia Yu Yiming Wu Qingfang Li Weiqi Hong Yang Yang Xiaoyi Hu Yanfei Yang Tianqi Lu Xia Zhao Xiawei Wei |
| author_facet | Meijia Yu Yiming Wu Qingfang Li Weiqi Hong Yang Yang Xiaoyi Hu Yanfei Yang Tianqi Lu Xia Zhao Xiawei Wei |
| author_sort | Meijia Yu |
| collection | DOAJ |
| description | Ovarian cancer is the tumor with the highest mortality among gynecological malignancies. Studies have confirmed that paclitaxel chemoresistance is associated with increased infiltration of tumor-associated macrophages (TAMs) in the microenvironment. Colony-stimulating factor 1 (CSF-1) receptor (CSF-1R) plays a key role in regulating the number and differentiation 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 tumor microenvironment. Here, we explored the antitumor efficacy and possible mechanisms of the CSF − 1R inhibitor pexidartinib (PLX3397) when combined with the first-line chemotherapeutic agent paclitaxel in the treatment of ovarian cancer. We found that CSF-1R is highly expressed 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. |
| first_indexed | 2024-03-07T21:43:25Z |
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| institution | Directory Open Access Journal |
| issn | 2352-3042 |
| language | English |
| last_indexed | 2024-03-07T21:43:25Z |
| publishDate | 2024-05-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Genes and Diseases |
| spelling | doaj.art-54afd353450a4c4ca987e67d9fb9b2a52024-02-26T04:15:45ZengKeAi Communications Co., Ltd.Genes and Diseases2352-30422024-05-01113100989Colony-stimulating factor-1 receptor inhibition combined with paclitaxel exerts effective antitumor effects in the treatment of ovarian cancerMeijia Yu0Yiming Wu1Qingfang Li2Weiqi Hong3Yang Yang4Xiaoyi Hu5Yanfei Yang6Tianqi Lu7Xia Zhao8Xiawei Wei9Laboratory 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; 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; Department of Obstetrics and Gynecology, The First Affiliated Hospital, Army Medical University, Chongqing 400038, ChinaLaboratory 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, ChinaLaboratory 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, ChinaLaboratory 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaLaboratory 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, ChinaDepartment 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; Corresponding author.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; Corresponding author.Ovarian cancer is the tumor with the highest mortality among gynecological malignancies. Studies have confirmed that paclitaxel chemoresistance is associated with increased infiltration of tumor-associated macrophages (TAMs) in the microenvironment. Colony-stimulating factor 1 (CSF-1) receptor (CSF-1R) plays a key role in regulating the number and differentiation 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 tumor microenvironment. Here, we explored the antitumor efficacy and possible mechanisms of the CSF − 1R inhibitor pexidartinib (PLX3397) when combined with the first-line chemotherapeutic agent paclitaxel in the treatment of ovarian cancer. We found that CSF-1R is highly expressed 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.http://www.sciencedirect.com/science/article/pii/S2352304223002349CSF-1ROvarian cancerPaclitaxelPLX3397Targeted therapyTumor-associated macrophages |
| spellingShingle | Meijia Yu Yiming Wu Qingfang Li Weiqi Hong Yang Yang Xiaoyi Hu Yanfei Yang Tianqi Lu Xia Zhao Xiawei Wei Colony-stimulating factor-1 receptor inhibition combined with paclitaxel exerts effective antitumor effects in the treatment of ovarian cancer Genes and Diseases CSF-1R Ovarian cancer Paclitaxel PLX3397 Targeted therapy Tumor-associated macrophages |
| title | Colony-stimulating factor-1 receptor inhibition combined with paclitaxel exerts effective antitumor effects in the treatment of ovarian cancer |
| title_full | Colony-stimulating factor-1 receptor inhibition combined with paclitaxel exerts effective antitumor effects in the treatment of ovarian cancer |
| title_fullStr | Colony-stimulating factor-1 receptor inhibition combined with paclitaxel exerts effective antitumor effects in the treatment of ovarian cancer |
| title_full_unstemmed | Colony-stimulating factor-1 receptor inhibition combined with paclitaxel exerts effective antitumor effects in the treatment of ovarian cancer |
| title_short | Colony-stimulating factor-1 receptor inhibition combined with paclitaxel exerts effective antitumor effects in the treatment of ovarian cancer |
| title_sort | colony stimulating factor 1 receptor inhibition combined with paclitaxel exerts effective antitumor effects in the treatment of ovarian cancer |
| topic | CSF-1R Ovarian cancer Paclitaxel PLX3397 Targeted therapy Tumor-associated macrophages |
| url | http://www.sciencedirect.com/science/article/pii/S2352304223002349 |
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