Foglizzo Valentina, Cocco Emiliano, Marchiò Serena
Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Department of Oncology, University of Torino, 10060 Candiolo, Italy.
Cancers (Basel). 2022 Jul 28;14(15):3692. doi: 10.3390/cancers14153692.
Cancer is a complex disease arising from a homeostatic imbalance of cell-intrinsic and microenvironment-related mechanisms. A multimodal approach to treat cancer that includes surgery, chemotherapy, and radiation therapy often fails in achieving tumor remission and produces unbearable side effects including secondary malignancies. Novel strategies have been implemented in the past decades in order to replace conventional chemotherapeutics with targeted, less toxic drugs. Up to now, scientists have relied on results achieved in animal research before proceeding to clinical trials. However, the high failure rate of targeted drugs in early phase trials leaves no doubt about the inadequacy of those models. In compliance with the need of reducing, and possibly replacing, animal research, studies have been conducted in vitro with advanced cellular models that more and more mimic the tumor in vivo. We will here review those methods that allow for the 3D reconstitution of the tumor and its microenvironment and the implementation of the organ-on-a-chip technology to study minimal organ units in disease progression. We will make specific reference to the usability of these systems as predictive cancer models and report on recent applications in high-throughput screenings of innovative and targeted drug compounds.
癌症是一种源于细胞内在机制与微环境相关机制稳态失衡的复杂疾病。包括手术、化疗和放疗在内的多模式癌症治疗方法往往无法实现肿瘤缓解，还会产生包括继发性恶性肿瘤在内的难以忍受的副作用。在过去几十年里，人们实施了新策略，用靶向性更强、毒性更低的药物取代传统化疗药物。到目前为止，科学家们在进行临床试验之前一直依赖于动物研究取得的结果。然而，靶向药物在早期试验中的高失败率无疑表明这些模型存在不足。为了满足减少甚至可能取代动物研究的需求，人们已经利用越来越能模拟体内肿瘤的先进细胞模型进行了体外研究。我们将在此回顾那些能够实现肿瘤及其微环境三维重建以及运用芯片器官技术研究疾病进展中最小器官单位的方法。我们将特别提及这些系统作为癌症预测模型的可用性，并报告其在创新型和靶向性药物化合物高通量筛选中的最新应用。
