Zhen Zeng, Hung Long Ngo, Martina Proctor, Helen Rizos, Riccardo Dolcetti, Jazmina Gonzalez Cruz, James W. Wells, Brian Gabrielli
{"title":"检查点激酶1抑制剂+小剂量羟基脲可有效杀死对BRAF抑制剂和免疫检查点抑制剂耐药的黑色素瘤。","authors":"Zhen Zeng, Hung Long Ngo, Martina Proctor, Helen Rizos, Riccardo Dolcetti, Jazmina Gonzalez Cruz, James W. Wells, Brian Gabrielli","doi":"10.1111/pcmr.13120","DOIUrl":null,"url":null,"abstract":"<p>Treatment of melanomas with targeted and immunotherapies has proven effective, but resistance to both treatments is a common outcome leaving a high proportion of patients without effective alternative treatment options. Replication stress is a common feature of melanomas, and this is effectively targeted using a combination of checkpoint kinase 1 (CHK1) inhibitor and low-dose hydroxyurea (LDHU). This combination also promotes inflammatory and anti-tumour immune responses in vivo. Melanoma cell lines resistant to BRAF inhibitor (BRAFi) or immune checkpoint inhibitors (ICI) retain their sensitivity to CHK1i + LDHU, with sensitivity similar to that of parental tumours. In vivo, BRAFi-resistant and BRAFi-sensitive parental tumours produce an identical immune response with treatment.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"37 1","pages":"45-50"},"PeriodicalIF":3.9000,"publicationDate":"2023-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/pcmr.13120","citationCount":"0","resultStr":"{\"title\":\"Checkpoint kinase 1 inhibitor + low-dose hydroxyurea efficiently kills BRAF inhibitor- and immune checkpoint inhibitor-resistant melanomas\",\"authors\":\"Zhen Zeng, Hung Long Ngo, Martina Proctor, Helen Rizos, Riccardo Dolcetti, Jazmina Gonzalez Cruz, James W. Wells, Brian Gabrielli\",\"doi\":\"10.1111/pcmr.13120\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Treatment of melanomas with targeted and immunotherapies has proven effective, but resistance to both treatments is a common outcome leaving a high proportion of patients without effective alternative treatment options. Replication stress is a common feature of melanomas, and this is effectively targeted using a combination of checkpoint kinase 1 (CHK1) inhibitor and low-dose hydroxyurea (LDHU). This combination also promotes inflammatory and anti-tumour immune responses in vivo. Melanoma cell lines resistant to BRAF inhibitor (BRAFi) or immune checkpoint inhibitors (ICI) retain their sensitivity to CHK1i + LDHU, with sensitivity similar to that of parental tumours. In vivo, BRAFi-resistant and BRAFi-sensitive parental tumours produce an identical immune response with treatment.</p>\",\"PeriodicalId\":219,\"journal\":{\"name\":\"Pigment Cell & Melanoma Research\",\"volume\":\"37 1\",\"pages\":\"45-50\"},\"PeriodicalIF\":3.9000,\"publicationDate\":\"2023-08-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1111/pcmr.13120\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pigment Cell & Melanoma Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/pcmr.13120\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pigment Cell & Melanoma Research","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/pcmr.13120","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
Treatment of melanomas with targeted and immunotherapies has proven effective, but resistance to both treatments is a common outcome leaving a high proportion of patients without effective alternative treatment options. Replication stress is a common feature of melanomas, and this is effectively targeted using a combination of checkpoint kinase 1 (CHK1) inhibitor and low-dose hydroxyurea (LDHU). This combination also promotes inflammatory and anti-tumour immune responses in vivo. Melanoma cell lines resistant to BRAF inhibitor (BRAFi) or immune checkpoint inhibitors (ICI) retain their sensitivity to CHK1i + LDHU, with sensitivity similar to that of parental tumours. In vivo, BRAFi-resistant and BRAFi-sensitive parental tumours produce an identical immune response with treatment.
期刊介绍：
Pigment Cell & Melanoma Researchpublishes manuscripts on all aspects of pigment cells including development, cell and molecular biology, genetics, diseases of pigment cells including melanoma. Papers that provide insights into the causes and progression of melanoma including the process of metastasis and invasion, proliferation, senescence, apoptosis or gene regulation are especially welcome, as are papers that use the melanocyte system to answer questions of general biological relevance. Papers that are purely descriptive or make only minor advances to our knowledge of pigment cells or melanoma in particular are not suitable for this journal. Keywords
Pigment Cell & Melanoma Research, cell biology, melatonin, biochemistry, chemistry, comparative biology, dermatology, developmental biology, genetics, hormones, intracellular signalling, melanoma, molecular biology, ocular and extracutaneous melanin, pharmacology, photobiology, physics, pigmentary disorders
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