Targeting the Tumor Stroma as a Novel Therapeutic Approach for Prostate Cancer
Targeting the Tumor Stroma as a Novel Therapeutic Approach for Prostate Cancer
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DOI：
10.1016/b978-0-12-397927-8.00009-9
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发表时间：
2012-01-01
期刊：
影响因子：
--
通讯作者：
Hayward, Simon W.
中科院分区：
文献类型：
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作者：
Franco, Omar E.;Hayward, Simon W.
上皮和周围基质之间的相互作用是维持器官功能所必需的。这些相互作用提供了由生长因子和细胞外基质成分介导的定义解剖学和位置信息的增殖和迁移限制。当癌症发展时，转化的细胞失去了这些限制，而基质适应并共同进化以支持肿瘤的“功能”。前列腺是在正常发育和癌症进展期间依赖于其周围基质的器官的一个很好的例子。癌相关成纤维细胞（CAF）构成了肿瘤基质的相当大的体积，并在肿瘤的维持，传播，甚至耐药性中发挥关键作用。CAF的起源及其促进肿瘤进展的确切机制仍有争议。CAF获得与在损伤部位的伤口修复期间观察到的非常相似的活化表型。在这里，我们描述了CAF的个体发生，在生理伤口修复过程中与活化的成纤维细胞的相似性，以及可以靶向防止其在肿瘤中出现的潜在途径及其在癌症进展中的促肿瘤功能。由于对组成肿瘤的细胞和组织之间的复杂相互作用的理解增加，识别用于治疗靶向的基质细胞生物学方面的策略变得越来越合理。一些临床前和临床研究表明，靶向基质可能是治疗癌症的一种有前途和有吸引力的治疗选择，并有可能在未来的治疗策略中发挥越来越重要的作用。
Interactions between epithelium and the surrounding stroma are required to maintain organ function. These interactions provide proliferative and migratory restraints that define anatomical and positional information, mediated by growth factors and extracellular matrix components. When cancer develops, transformed cells lose these constraints while stroma adapts and coevolves to support the "function" of the tumor. The prostate is a good example of an organ that relies on its surrounding stroma during normal development and cancer progression. Carcinoma-associated fibroblasts (CAFs) constitute a substantial volume of the tumor stroma and play a pivotal role in tumor maintenance, dissemination, and even drug resistance. The origins of CAF and the exact mechanisms by which they promote tumor progression are still debated. CAF acquire an activated phenotype quite similar to the one seen during wound repair in sites of injury. Here, we describe the CAF ontogeny, the similarities with activated fibroblasts during physiological wound repair, and potential pathways that can be targeted to prevent their appearance in tumors and their protumorigenic functions in cancer progression. A strategy to identify aspects of stromal cell biology for therapeutic targeting is becoming increasingly plausible, driven by the increased understanding of the complex interplays between the cells and tissues of which tumors are comprised. Several preclinical and clinical studies show that targeting the stroma may be a promising and attractive therapeutic option for the treatment of cancer and has the potential to play an increasingly prominent role in future treatment strategies.