1 Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
2 Cancer Science Institute of Singapore, National University of Singapore, Singapore.
SLAS Technol. 2017 Jun;22(3):245-253. doi: 10.1177/2472630317697251. Epub 2017 Mar 9.
Advances in understanding many of the fundamental mechanisms of cancer progression have led to the development of molecular targeted therapies. While molecular targeted therapeutics continue to improve the outcome for cancer patients, tumor heterogeneity among patients, as well as intratumoral heterogeneity, limits the efficacy of these drugs to specific patient subtypes, as well as contributes to relapse. Thus, there is a need for a more personalized approach toward drug development and diagnosis that takes into account the diversity of cancer patients, as well as the complex milieu of tumor cells within a single patient. Three-dimensional (3D) culture systems paired with patient-derived xenografts or patient-derived organoids may provide a more clinically relevant system to address issues presented by personalized or precision medical approaches. In this review, we cover the current methods available for applying 3D culture systems toward personalized cancer research and drug development, as well as key challenges that must be addressed in order to fully realize the potential of 3D patient-derived culture systems for cancer drug development. Greater implementation of 3D patient-derived culture systems in the cancer research field should accelerate the development of truly personalized medical therapies for cancer patients.
对癌症进展的许多基本机制的深入了解,促使了分子靶向治疗的发展。虽然分子靶向治疗继续改善了癌症患者的预后,但患者之间的肿瘤异质性以及肿瘤内异质性限制了这些药物对特定患者亚型的疗效,并导致了复发。因此,需要一种更加个性化的药物开发和诊断方法,考虑到癌症患者的多样性,以及单个患者中肿瘤细胞的复杂环境。与患者来源的异种移植物或患者来源的类器官相结合的三维(3D)培养系统可能为解决个性化或精准医疗方法所带来的问题提供更具临床相关性的系统。在这篇综述中,我们介绍了目前可用于将 3D 培养系统应用于个性化癌症研究和药物开发的方法,以及为充分发挥 3D 患者来源培养系统在癌症药物开发中的潜力而必须解决的关键挑战。在癌症研究领域中,更多地应用 3D 患者来源的培养系统,将加速为癌症患者开发真正的个性化医疗疗法。