Oklahoma Medical Research Foundation, Aging and Metabolism Research Program, Oklahoma City, OK 73104, USA.
Oncotarget. 2022 Mar 24;13:553-575. doi: 10.18632/oncotarget.28220. eCollection 2022.
Despite advances in understanding of ovarian cancer biology, the progress in translation of research findings into new therapies is still slow. It is associated in part with limitations of commonly used cancer models such as cell lines and genetically engineered mouse models that lack proper representation of diversity and complexity of actual human tumors. In addition, the development of anticancer drugs is a lengthy and expensive process. A promising alternative to new drug development is repurposing existing FDA-approved drugs without primary oncological purpose. These approved agents have known pharmacokinetics, pharmacodynamics, and toxicology and could be approved as anticancer drugs quicker and at lower cost. To successfully translate repurposed drugs to clinical application, an intermediate step of pre-clinical animal studies is required. To address challenges associated with reliability of tumor models for pre-clinical studies, there has been an increase in development of patient-derived xenografts (PDXs), which retain key characteristics of the original patient's tumor, including histologic, biologic, and genetic features. The expansion and utilization of clinically and molecularly annotated PDX models derived from different ovarian cancer subtypes could substantially aid development of new therapies or rapid approval of repurposed drugs to improve treatment options for ovarian cancer patients.
尽管对卵巢癌生物学的认识有所进展，但将研究发现转化为新疗法的进展仍然缓慢。部分原因是常用的癌症模型（如细胞系和基因工程小鼠模型）存在局限性，这些模型缺乏对实际人类肿瘤多样性和复杂性的适当代表性。此外，抗癌药物的开发是一个漫长而昂贵的过程。替代新药开发的一个有前途的方法是重新利用现有的美国食品和药物管理局（FDA）批准的、没有主要肿瘤学用途的药物。这些已批准的药物具有已知的药代动力学、药效学和毒理学特性，并且可以更快、更低成本地被批准为抗癌药物。为了成功地将重新利用的药物转化为临床应用，需要进行临床前动物研究的中间步骤。为了解决肿瘤模型在临床前研究中的可靠性相关挑战，已经增加了患者来源的异种移植（PDX）的开发，这些移植保留了原始患者肿瘤的关键特征，包括组织学、生物学和遗传特征。从不同的卵巢癌亚型中衍生的具有临床和分子注释的 PDX 模型的扩展和利用，可以极大地帮助新疗法的开发或重新利用药物的快速批准，从而改善卵巢癌患者的治疗选择。
