Phenotype-driven precision oncology as a guide for clinical decisions one patient at a time

Nat Commun. 2017 Sep 5;8(1):435. doi: 10.1038/s41467-017-00451-5.


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.

Trial registration: NCT02806388.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Animals
  • Biomarkers, Tumor
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / pathology
  • Cisplatin / pharmacology
  • Drug Resistance, Neoplasm
  • Gefitinib
  • Gene Expression Regulation, Neoplastic*
  • Head and Neck Neoplasms / drug therapy*
  • Head and Neck Neoplasms / genetics
  • Head and Neck Neoplasms / pathology
  • Humans
  • Mice, Inbred NOD
  • Mouth Neoplasms / drug therapy
  • Mouth Neoplasms / genetics
  • Mouth Neoplasms / pathology
  • Phenotype
  • Phosphoproteins / genetics
  • Precision Medicine / methods*
  • Quinazolines / pharmacology
  • Transcription Factors
  • Treatment Outcome
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays


  • Adaptor Proteins, Signal Transducing
  • Biomarkers, Tumor
  • Phosphoproteins
  • Quinazolines
  • Transcription Factors
  • YAP1 (Yes-associated) protein, human
  • Cisplatin
  • Gefitinib

Associated data