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Phenotype-driven precision oncology as a guide for clinical decisions one patient at a time
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Journal Article
Phenotype-driven precision oncology as a guide for clinical decisions one patient at a time
2017
Overview
Genomics-driven cancer therapeutics has gained prominence in personalized cancer treatment. However, its utility in indications lacking biomarker-driven treatment strategies remains limited. Here we present a “phenotype-driven precision-oncology” approach, based on the notion that biological response to perturbations, chemical or genetic, in ex vivo patient-individualized models can serve as predictive biomarkers for therapeutic response in the clinic. We generated a library of “screenable” patient-derived primary cultures (PDCs) for head and neck squamous cell carcinomas that reproducibly predicted treatment response in matched patient-derived-xenograft models. Importantly, PDCs could guide clinical practice and predict tumour progression in two
n
= 1 co-clinical trials. Comprehensive “-omics” interrogation of PDCs derived from one of these models revealed YAP1 as a putative biomarker for treatment response and survival in ~24% of oral squamous cell carcinoma. We envision that scaling of the proposed PDC approach could uncover biomarkers for therapeutic stratification and guide real-time therapeutic decisions in the future.
Treatment response in patient-derived models may serve as a biomarker for response in the clinic. Here, the authors use paired patient-derived mouse xenografts and patient-derived primary culture models from head and neck squamous cell carcinomas, including metastasis, as models for high-throughput screening of anti-cancer drugs.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ Adaptor Proteins, Signal Transducing - genetics
/ Animals
/ Cancer
/ Carcinoma, Squamous Cell - drug therapy
/ Carcinoma, Squamous Cell - genetics
/ Carcinoma, Squamous Cell - pathology
/ Gene Expression Regulation, Neoplastic
/ Head
/ Head and Neck Neoplasms - drug therapy
/ Head and Neck Neoplasms - genetics
/ Head and Neck Neoplasms - pathology
/ Humanities and Social Sciences
/ Humans
/ Mouth Neoplasms - drug therapy
/ Precision Medicine - methods
/ Science
