Modeling prostate cancer: What does it take to build an ideal tumor model?
Modeling prostate cancer: What does it take to build an ideal tumor model?
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前列腺癌建模：建立理想的肿瘤模型需要什么？
DOI：
10.1016/j.canlet.2022.215794
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发表时间：
2022-09-01
期刊：
影响因子：
9.7
通讯作者：
Chua, Chee Wai
中科院分区：
文献类型：
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作者：
Mai, Chun-Wai;Chin, Kok-Yong;Chua, Chee Wai
前列腺癌是一种多灶性疾病，具有很大的瘤内异质性和很高的骨转移倾向。因此，对这一领域的研究人员来说，前列腺癌的建模一直是一项具有挑战性的任务。在过去的几十年里，基因组的进步导致了前列腺癌关键分子变化的识别。此外，对第二代雄激素剥夺疗法，即阿比特龙和苯扎鲁胺的抵抗，揭示了具有独特组织病理学和临床特征的雄激素受体非依赖性疾病。在这篇综述中，我们对常用的前列腺癌临床前模型进行了批判性的评估，评价了它们概括人类前列腺癌的关键基因组改变、组织病理学特征和骨转移潜能的能力。此外，我们还讨论了新出现的器官模型在前列腺癌研究中的潜在应用，这些模型比常用的临床前肿瘤模型具有明显的优势。我们预计，没有一个单一的模型能够真实地概括前列腺癌的复杂性，因此，我们建议使用一种成本和时间效率高的综合肿瘤建模方法来进行未来的前列腺癌研究。
Prostate cancer is frequently characterized as a multifocal disease with great intratumoral heterogeneity as well as a high propensity to metastasize to bone. Consequently, modeling prostate tumor has remained a challenging task for researchers in this field. In the past decades, genomic advances have led to the identification of key molecular alterations in prostate cancer. Moreover, resistance towards second-generation androgen-deprivation therapy, namely abiraterone and enzalutamide has unveiled androgen receptor-independent diseases with distinctive histopathological and clinical features. In this review, we have critically evaluated the commonly used preclinical models of prostate cancer with respect to their capability of recapitulating the key genomic alterations, histopathological features and bone metastatic potential of human prostate tumors. In addition, we have also discussed the potential use of the emerging organoid models in prostate cancer research, which possess clear advantages over the commonly used preclinical tumor models. We anticipate that no single model can faithfully recapitulate the complexity of prostate cancer, and thus, propose the use of a cost- and time-efficient integrated tumor modeling approach for future prostate cancer investigations.