Department of Biological Chemistry, School of Sciences, University of Buenos Aires, Ciudad Universitaria, Pabellón II, Buenos Aires, Argentina-CONICET.
Prostate Cancer Prostatic Dis. 2012 Sep;15(3):213-21. doi: 10.1038/pcan.2011.64. Epub 2011 Dec 20.
It is currently estimated that inflammatory responses are linked to 15-20% of all deaths from cancer worldwide. Although many studies point to an important role of inflammation in prostate growth, the contribution of inflammation to castration-resistant prostate cancer is not completely understood. The presence of inflammatory mediators in tumor microenvironment raises the question whether genetic events that participate in cancer development and progression are responsible for the inflammatory milieu inside and surrounding tumors. Activated oncogenes, cytokines, chemokines and their receptors, sustained oxidative stress and antioxidant imbalance share the capacity to orchestrate these pro-inflammatory programs; however, the diversity of the inflammatory cell components will determine the final response in the prostate tissue. These observations give rise to the concept that early genetic events generate an inflammatory microenvironment promoting prostate cancer progression and creating a continuous loop that stimulates a more aggressive stage. It is imperative to dissect the molecular pathologic mechanism of inflammation involved in the generation of the castration-resistant phenotype in prostate cancer. Here, we present a hypothesis where molecular signaling triggered by inflammatory mediators may evolve in prostate cancer progression. Thus, treatment of chronic inflammation may represent an important therapeutic target in advanced prostate cancer.
目前估计，炎症反应与全球 15-20%的癌症死亡有关。尽管许多研究指出炎症在前列腺生长中的重要作用，但炎症对去势抵抗性前列腺癌的贡献尚不完全清楚。肿瘤微环境中炎症介质的存在提出了一个问题，即参与癌症发展和进展的遗传事件是否负责肿瘤内部和周围的炎症环境。激活的癌基因、细胞因子、趋化因子及其受体、持续的氧化应激和抗氧化失衡都有能力协调这些促炎程序；然而，炎症细胞成分的多样性将决定前列腺组织的最终反应。这些观察结果提出了一个概念，即早期遗传事件产生炎症微环境，促进前列腺癌的进展，并形成一个连续的循环，刺激更具侵袭性的阶段。剖析炎症在前列腺癌去势抵抗表型产生中所涉及的分子病理机制至关重要。在这里，我们提出了一个假设，即炎症介质触发的分子信号可能在前列腺癌进展中进化。因此，治疗慢性炎症可能是晚期前列腺癌的一个重要治疗靶点。
