The Androgen Regulation of Matrix Metalloproteases in Prostate Cancer and Its Related Tumor Microenvironment

Carmela Sorrentino, Rosa D’Angiolo, Giulia Gentile, P. Giovannelli, B. Perillo, A. Migliaccio, G. Castoria, M. Di Donato
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Abstract

Prostate cancer represents the most common type of cancer among males and the second leading cause of cancer death in men in Western society. In most cases (~70%), PC has a slow and symptom-free growth, whereas it is more aggressive in the remaining patients. Current PC therapies prevalently target the proliferative function of the androgen receptor and may only be effective within short periods, beyond which the disease will progress to metastatic and castration-resistant phenotype. Preclinical and clinical studies are aimed at investigating the molecular basis for prostate cancer spreading. Although considerable efforts have been made to dissect the programs that foster prostate cancer spreading, few biomarkers predictive of metastatic phenotype have yet been identified and few therapeutic options are available for treatment of the metastatic disease. In the present paper, we will discuss innovative aspects of prostate cancer biology, which impinge on the role of cancer-associated fibroblasts and the released matrix metalloproteinases in the disease progression. Investigating these aspects might allow the discovery of clinically actionable biomarkers to target in the advanced stages of prostate cancer.
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基质金属蛋白酶在前列腺癌症及其相关肿瘤微环境中的雄激素调节
前列腺癌症是男性中最常见的癌症类型,也是西方社会男性癌症死亡的第二大原因。在大多数情况下(约70%),PC生长缓慢且无症状,而在其余患者中则更具攻击性。目前的PC治疗主要针对雄激素受体的增殖功能,可能仅在短期内有效,超过短期,疾病将发展为转移性和去势抗性表型。临床前和临床研究旨在研究癌症扩散的分子基础。尽管已经做出了相当大的努力来剖析促进癌症扩散的程序,但很少有预测转移表型的生物标志物被确定,也很少有治疗转移性疾病的治疗选择。在本论文中,我们将讨论前列腺癌症生物学的创新方面,这些方面影响了癌症相关成纤维细胞和释放的基质金属蛋白酶在疾病进展中的作用。研究这些方面可能有助于发现临床上可操作的靶向癌症晚期的生物标志物。
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