Patient-Derived Xenografts for Prognostication and Personalized Treatment for Head and Neck Squamous Cell Carcinoma

Cell Rep. 2018 Oct 30;25(5):1318-1331.e4. doi: 10.1016/j.celrep.2018.10.004.


Overall survival remains very poor for patients diagnosed as having head and neck squamous cell carcinoma (HNSCC). Identification of additional biomarkers and novel therapeutic strategies are important for improving patient outcomes. Patient-derived xenografts (PDXs), generated by implanting fresh tumor tissue directly from patients into immunodeficient mice, recapitulate many of the features of their corresponding clinical cancers, including histopathological and molecular profiles. Using a large collection of PDX models of HNSCC, we demonstrate that rapid engraftment into immunocompromised mice is highly prognostic and show that genomic deregulation of the G1/S checkpoint pathway correlates with engraftment. Furthermore, CCND1 and CDKN2A genomic alterations are predictive of response to the CDK4and CDK6 inhibitor abemaciclib. Overall, our study supports the pursuit of CDK4 and CDK6 inhibitors as a therapeutic strategy for a substantial proportion of HNSCC patients and demonstrates the potential of using PDX models to identify targeted therapies that will benefit patients who have the poorest outcomes.

Keywords: abemaciclib; cyclin D1; engraftment; head and neck squamous cell carcinoma; patient-derived xenografts; preclinical drug testing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminopyridines / pharmacology
  • Aminopyridines / therapeutic use
  • Animals
  • Base Sequence
  • Benzimidazoles / pharmacology
  • Benzimidazoles / therapeutic use
  • Cyclin D1 / genetics
  • Cyclin-Dependent Kinase 4 / metabolism
  • Cyclin-Dependent Kinase 6 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • Female
  • Humans
  • Male
  • Mice, Inbred NOD
  • Mice, SCID
  • Middle Aged
  • Multivariate Analysis
  • Mutation / genetics
  • Neoplasm Recurrence, Local / pathology
  • Precision Medicine*
  • Prognosis
  • Regression Analysis
  • Risk Factors
  • Squamous Cell Carcinoma of Head and Neck / drug therapy
  • Squamous Cell Carcinoma of Head and Neck / genetics
  • Squamous Cell Carcinoma of Head and Neck / pathology
  • Squamous Cell Carcinoma of Head and Neck / therapy*
  • Survival Analysis
  • Treatment Outcome
  • Xenograft Model Antitumor Assays*


  • Aminopyridines
  • Benzimidazoles
  • CCND1 protein, human
  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclin D1
  • abemaciclib
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinase 6