Inflammation as a Driver of Prostate Cancer Metastasis and Therapeutic Resistance.
Inflammation as a Driver of Prostate Cancer Metastasis and Therapeutic Resistance.
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DOI：
10.3390/cancers12102984
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发表时间：
2020-10-15
期刊：
影响因子：
5.2
通讯作者：
Kyprianou N
中科院分区：
文献类型：
--
作者：
Archer M;Dogra N;Kyprianou N
前列腺癌是男性最常见的恶性肿瘤，当疾病进展到转移和治疗耐药时死亡率很高。有证据表明炎症是前列腺癌风险的一个驱动因素，并对肿瘤微环境中促进进展为晚期治疗耐药性疾病的过程产生重大影响。在这篇综述中，我们讨论了前列腺炎症的来源、关键炎症效应物对前列腺癌发生和转移进展的功能贡献，以及它们对晚期疾病的治疗和克服治疗耐药带来的治疗挑战。充分了解炎症在前列腺癌进展为晚期转移性疾病和肿瘤复发中的作用将有助于开发个性化预测生物标志物和治疗方法，以减轻前列腺癌患者的负担和死亡率。前列腺癌是男性中最常见的恶性肿瘤，进展到转移和出现治疗耐药性疾病导致死亡率很高。越来越多的证据表明炎症是前列腺癌发生和进展的驱动因素，导致前列腺癌的风险增加。基于人群的研究表明，使用抗炎药物可使前列腺癌发生风险降低 23%，这种负相关性在专门使用 COX-2 抑制剂的男性中更为明显。此外，服用阿司匹林的患者患前列腺癌的风险降低了 21%，此外，与对照组相比，长期每日服用低剂量阿司匹林的患者患前列腺癌的风险降低了 29%。细菌和病毒感染的环境暴露、诱变剂的暴露以及遗传变异使前列腺容易发生炎症，并导致炎症细胞因子（IL-6、TGF-β）表达协调升高。肿瘤微环境中的动态使这些细胞因子能够促进原发肿瘤的存活和生长，并通过免疫调节网络、表型上皮间质转化（EMT）、血管生成、失巢凋亡抵抗和转移来促进疾病进展。在这篇综述中，我们讨论了前列腺炎症的来源、关键炎症效应物对前列腺癌发生和转移进展的功能贡献，以及它们对晚期疾病的治疗和克服治疗耐药带来的治疗挑战。越来越多的机制证据支持炎症在局限性前列腺癌中的重要性，以及肿瘤微环境内的过程对晚期耐药前列腺癌疾病进展的系统性影响。严格利用炎症在前列腺癌进展为转移和治疗耐药中的作用，将有助于开发精确的生物标志物特征和有效的靶向治疗方法，以减少未来的临床负担和致命疾病。
Prostate cancer is the most common malignancy in men, with a high mortality rate when disease progresses to metastasis and therapeutic resistance. Evidence implicates inflammation as a driver of prostate cancer risk and has a significant impact on processes in the tumor microenvironment that facilitate progression to advanced therapeutically resistant disease. In this review, we discuss the sources of inflammation in the prostate, the functional contribution of the critical inflammatory effectors to prostate cancer initiation and metastatic progression, and the therapeutic challenges that they impose on treatment of advanced disease and overcoming therapeutic resistance. Full understanding of the role of inflammation in prostate cancer progression to advanced metastatic disease and tumor relapse will aid in the development of personalized predictive biomarkers and therapy to reduce the burden and mortality in prostate cancer patients. Prostate cancer is the most common malignancy among men, and progression to metastasis and the emergence of therapeutically resistant disease confers a high mortality rate. Growing evidence implicates inflammation as a driver of prostate cancer development and progression, resulting in increased cancer risk for prostate cancer. Population-based studies revealed that the use of antinflammatory drugs led to a 23% risk reduction prostate cancer occurrence, a negative association that was stronger in men who specifically used COX-2 inhibitors. Furthermore, patients that were taking aspirin had a 21% reduction in prostate cancer risk, and further, long-term users of daily low dose aspirin had a 29% prostate cancer risk reduction as compared to the controls. Environmental exposure to bacterial and viral infections, exposure to mutagenic agents, and genetic variations predispose the prostate gland to inflammation, with a coordinated elevated expression of inflammatory cytokines (IL-6, TGF-β). It is the dynamics within the tumor microenvironment that empower these cytokines to promote survival and growth of the primary tumor and facilitate disease progression by navigating the immunoregulatory network, phenotypic epithelial-mesenchymal transition (EMT), angiogenesis, anoikis resistance, and metastasis. In this review, we discuss the sources of inflammation in the prostate, the functional contribution of the critical inflammatory effectors to prostate cancer initiation and metastatic progression, and the therapeutic challenges that they impose on treatment of advanced disease and overcoming therapeutic resistance. Growing mechanistic evidence supports the significance of inflammation in localized prostate cancer, and the systemic impact of the process within the tumor microenvironment on disease progression to advanced therapeutically-resistant prostate cancer. Rigorous exploitation of the role of inflammation in prostate cancer progression to metastasis and therapeutic resistance will empower the development of precise biomarker signatures and effective targeted therapeutics to reduce the clinical burden and lethal disease in the future.
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影响因子：
45.3
作者：
Antonarakis, Emmanuel S.;Heath, Elisabeth I.;Carducci, Michael A.
通讯作者：
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影响因子：
5.4
作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1016/j.urolonc.2017.01.020
发表时间：
2017-05-01
影响因子：
2.7
作者：
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通讯作者：
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