Oncology Research Centre, Prince of Wales Hospital, Barker St., Randwick, NSW, 2031, Australia.
Cancer Metastasis Rev. 2010 Mar;29(1):123-42. doi: 10.1007/s10555-010-9212-9.
Despite considerable success in treatment of early stage localized prostate cancer (PC), acute inadequacy of late stage PC treatment and its inherent heterogeneity poses a formidable challenge. Clearly, an improved understanding of PC genesis and progression along with the development of new targeted therapies are warranted. Animal models, especially, transgenic immunocompetent mouse models, have proven to be the best ally in this respect. A series of models have been developed by modulation of expression of genes implicated in cancer-genesis and progression; mainly, modulation of expression of oncogenes, steroid hormone receptors, growth factors and their receptors, cell cycle and apoptosis regulators, and tumor suppressor genes have been used. Such models have contributed significantly to our understanding of the molecular and pathological aspects of PC initiation and progression. In particular, the transgenic mouse models based on multiple genetic alterations can more accurately address the inherent complexity of PC, not only in revealing the mechanisms of tumorigenesis and progression but also for clinically relevant evaluation of new therapies. Further, with advances in conditional knockout technologies, otherwise embryonically lethal gene changes can be incorporated leading to the development of new generation transgenics, thus adding significantly to our existing knowledge base. Different models and their relevance to PC research are discussed.
尽管在治疗早期局限性前列腺癌 (PC) 方面取得了相当大的成功，但晚期 PC 治疗的急性不足及其固有的异质性仍然构成了严峻的挑战。显然，需要更好地了解 PC 的发生和发展，并开发新的靶向治疗方法。在这方面，动物模型，特别是转基因免疫功能正常的小鼠模型，已被证明是最好的盟友。通过调节与癌症发生和发展相关的基因的表达，已经开发出一系列模型；主要是，调节癌基因、甾体激素受体、生长因子及其受体、细胞周期和凋亡调节剂以及肿瘤抑制基因的表达。这些模型为我们理解 PC 起始和发展的分子和病理方面做出了重大贡献。特别是，基于多种遗传改变的转基因小鼠模型可以更准确地解决 PC 的固有复杂性，不仅可以揭示肿瘤发生和发展的机制，还可以对新疗法进行临床相关评估。此外，随着条件性基因敲除技术的进步，原本在胚胎期就会致死的基因变化也可以被引入，从而开发出新一代的转基因动物，从而大大增加了我们现有的知识库。讨论了不同的模型及其与 PC 研究的相关性。
