David J J Waugh, Jacqui A McGovern, Suzanne McCusker
{"title":"靶向细胞因子和趋化因子驱动的炎症信号在转移性去势抵抗性前列腺癌中的挑战和新机遇。","authors":"David J J Waugh, Jacqui A McGovern, Suzanne McCusker","doi":"10.1615/CritRevOncog.2022043441","DOIUrl":null,"url":null,"abstract":"<p><p>Inflammation is a key risk factor and functional driver in the initiation and progression of prostate cancer (PCa). De-regulated cytokine and chemokine signaling facilitates critical communication between tumor cells and multiple cell lineages within the tumor microenvironment (TME). Historical attempts at using targeted approaches to disrupt inflammation have been disappointing, with sub-optimal or negligible clinical benefit. Our increased awareness of the myeloid infiltrate in supporting the acquisition of castrate resistance and underpinning the abject response of advanced PCa to immunotherapy has re-focused attention on improved strategies to disrupt these complex cytokine and chemokine signaling networks within the TME. These ongoing and prospective strategies are principally focused on employing cytokine-/chemokine-directed therapies in informed combination with androgen signaling inhibitors or immunotherapeutic agents and, increasingly, with due consideration of the genetic context of the tumor. The availability of molecular-targeted therapeutic agents directed against the critical signal transduction nodes activated by cytokine and chemokine signaling in tumor cells provides opportunities to reduce the impacts of biological redundancy. Precision-based trials that deploy this latest generation of cytokine- and chemokine-directed therapeutics, directed to enriched patient cohorts in a biologically informed and biomarker-guided manner, have the potential to diversify the armamentarium of agents that is required in order to transform long-term outcomes for a currently incurable and genetically heterogenous disease.</p>","PeriodicalId":35617,"journal":{"name":"Critical Reviews in Oncogenesis","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"2","resultStr":"{\"title\":\"The Challenges and Emerging Opportunities of Targeting Cytokines and Chemokine-Driven Inflammatory Signals in Metastatic Castrate-Resistant Prostate Cancer.\",\"authors\":\"David J J Waugh, Jacqui A McGovern, Suzanne McCusker\",\"doi\":\"10.1615/CritRevOncog.2022043441\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Inflammation is a key risk factor and functional driver in the initiation and progression of prostate cancer (PCa). De-regulated cytokine and chemokine signaling facilitates critical communication between tumor cells and multiple cell lineages within the tumor microenvironment (TME). Historical attempts at using targeted approaches to disrupt inflammation have been disappointing, with sub-optimal or negligible clinical benefit. Our increased awareness of the myeloid infiltrate in supporting the acquisition of castrate resistance and underpinning the abject response of advanced PCa to immunotherapy has re-focused attention on improved strategies to disrupt these complex cytokine and chemokine signaling networks within the TME. These ongoing and prospective strategies are principally focused on employing cytokine-/chemokine-directed therapies in informed combination with androgen signaling inhibitors or immunotherapeutic agents and, increasingly, with due consideration of the genetic context of the tumor. The availability of molecular-targeted therapeutic agents directed against the critical signal transduction nodes activated by cytokine and chemokine signaling in tumor cells provides opportunities to reduce the impacts of biological redundancy. Precision-based trials that deploy this latest generation of cytokine- and chemokine-directed therapeutics, directed to enriched patient cohorts in a biologically informed and biomarker-guided manner, have the potential to diversify the armamentarium of agents that is required in order to transform long-term outcomes for a currently incurable and genetically heterogenous disease.</p>\",\"PeriodicalId\":35617,\"journal\":{\"name\":\"Critical Reviews in Oncogenesis\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2022-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"2\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Critical Reviews in Oncogenesis\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1615/CritRevOncog.2022043441\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"Biochemistry, Genetics and Molecular Biology\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Critical Reviews in Oncogenesis","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1615/CritRevOncog.2022043441","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"Biochemistry, Genetics and Molecular Biology","Score":null,"Total":0}
The Challenges and Emerging Opportunities of Targeting Cytokines and Chemokine-Driven Inflammatory Signals in Metastatic Castrate-Resistant Prostate Cancer.
Inflammation is a key risk factor and functional driver in the initiation and progression of prostate cancer (PCa). De-regulated cytokine and chemokine signaling facilitates critical communication between tumor cells and multiple cell lineages within the tumor microenvironment (TME). Historical attempts at using targeted approaches to disrupt inflammation have been disappointing, with sub-optimal or negligible clinical benefit. Our increased awareness of the myeloid infiltrate in supporting the acquisition of castrate resistance and underpinning the abject response of advanced PCa to immunotherapy has re-focused attention on improved strategies to disrupt these complex cytokine and chemokine signaling networks within the TME. These ongoing and prospective strategies are principally focused on employing cytokine-/chemokine-directed therapies in informed combination with androgen signaling inhibitors or immunotherapeutic agents and, increasingly, with due consideration of the genetic context of the tumor. The availability of molecular-targeted therapeutic agents directed against the critical signal transduction nodes activated by cytokine and chemokine signaling in tumor cells provides opportunities to reduce the impacts of biological redundancy. Precision-based trials that deploy this latest generation of cytokine- and chemokine-directed therapeutics, directed to enriched patient cohorts in a biologically informed and biomarker-guided manner, have the potential to diversify the armamentarium of agents that is required in order to transform long-term outcomes for a currently incurable and genetically heterogenous disease.
期刊介绍:
The journal is dedicated to extensive reviews, minireviews, and special theme issues on topics of current interest in basic and patient-oriented cancer research. The study of systems biology of cancer with its potential for molecular level diagnostics and treatment implies competence across the sciences and an increasing necessity for cancer researchers to understand both the technology and medicine. The journal allows readers to adapt a better understanding of various fields of molecular oncology. We welcome articles on basic biological mechanisms relevant to cancer such as DNA repair, cell cycle, apoptosis, angiogenesis, tumor immunology, etc.