Lee Tet Woo, Lai Amy, Harms Julia K, Singleton Dean C, Dickson Benjamin D, Macann Andrew M J, Hay Michael P, Jamieson Stephen M F
Auckland Cancer Society Research Centre, University of Auckland, Auckland 1023, New Zealand.
Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland, Auckland 1010, New Zealand.
Cancers (Basel). 2020 Dec 12;12(12):3743. doi: 10.3390/cancers12123743.
Patient survival from head and neck squamous cell carcinoma (HNSCC), the seventh most common cause of cancer, has not markedly improved in recent years despite the approval of targeted therapies and immunotherapy agents. Precision medicine approaches that seek to individualise therapy through the use of predictive biomarkers and stratification strategies offer opportunities to improve therapeutic success in HNSCC. To enable precision medicine of HNSCC, an understanding of the microenvironment that influences tumour growth and response to therapy is required alongside research tools that recapitulate the features of human tumours. In this review, we highlight the importance of the tumour microenvironment in HNSCC, with a focus on tumour hypoxia, and discuss the fidelity of patient-derived xenograft and organoids for modelling human HNSCC and response to therapy. We describe the benefits of patient-derived models over alternative preclinical models and their limitations in clinical relevance and how these impact their utility in precision medicine in HNSCC for the discovery of new therapeutic agents, as well as predictive biomarkers to identify patients' most likely to respond to therapy.
头颈部鳞状细胞癌（HNSCC）是第七大常见癌症，尽管近年来靶向治疗和免疫治疗药物已获批准，但患者生存率并未显著提高。通过使用预测性生物标志物和分层策略来实现个体化治疗的精准医学方法，为提高HNSCC的治疗成功率提供了机会。为了实现HNSCC的精准医学，除了需要能够重现人类肿瘤特征的研究工具外，还需要了解影响肿瘤生长和对治疗反应的微环境。在本综述中，我们强调了肿瘤微环境在HNSCC中的重要性，重点关注肿瘤缺氧，并讨论了患者来源的异种移植模型和类器官在模拟人类HNSCC及治疗反应方面的逼真度。我们描述了患者来源模型相对于其他临床前模型的优势，以及它们在临床相关性方面的局限性，以及这些如何影响它们在HNSCC精准医学中发现新治疗药物以及识别最可能对治疗有反应的患者的预测性生物标志物方面的效用。
