基于肿瘤临床前模型建立头颈癌新型药物基因组学的必要性及展望

Establishing the novel pharmacogenomics of head and neck cancer based on preclinical tumor models: necessity and prospect

头颈癌是全球第七大恶性肿瘤类型,超过60%患者初次确诊即为中晚期。靶向治疗和免疫治疗的发展已经显著推动了头颈癌治疗策略的转型,但是临床获益有待进一步提升。肿瘤临床前模型保留了患者肿瘤的基因和表型的异质性,已广泛应用于临床前药物筛选和验证体系。药物基因组学通过将基因组学和药物响应进行匹配,能够基于肿瘤异质性基础进行患者分层,优化治疗策略并挖掘新治疗靶点。本文概述药物基因组学的发展史,从头颈癌治疗现状和异质性特征出发,探讨借助临床前模型开展新型药物基因组学的必要性和可行性。

Head and neck cancer is the seventh common malignant tumor in the world. For more than 60% patients, the diagnosis is made at an intermediate or advanced stage. Although the development of targeted therapy and immunotherapy has significantly promoted the transformation of therapeutic strategies of head and neck cancer, there is still an urgent need to expand the clinical benefits. Preclinical models of cancer, which maintain the genetic and phenotypic heterogeneity from their parental tumors, have been widely used in the preclinical drug screening and validation. By matching genomics and drug response, pharmacogenomics can stratify patients based on tumor heterogeneity, optimize treatment strategies, and discover new therapeutic targets. This paper outlines the history of pharmacogenomics, and discusses the necessity and feasibility of developing pharmacogenomics with the aid of preclinical models in the context of the current treatment status and tumor heterogeneity of head and neck cancer.