Patient Derived Models to Study Head and Neck Cancer Radiation Response

Abstract

Patient-derived model systems are important tools for studying novel anti-cancer therapies. Patient-derived xenografts (PDXs) have gained favor over the last 10 years as newer mouse strains have improved the success rate of establishing PDXs from patient biopsies. PDXs can be engrafted from head and neck cancer (HNC) samples across a wide range of cancer stages, retain the genetic features of their human source, and can be treated with both chemotherapy and radiation, allowing for clinically relevant studies. Not only do PDXs allow for the study of patient tissues in an in vivo model, they can also provide a renewable source of cancer cells for organoid cultures. Herein, we review the uses of HNC patient-derived models for radiation research, including approaches to establishing both orthotopic and heterotopic PDXs, approaches and potential pitfalls to delivering chemotherapy and radiation to these animal models, biological advantages and limitations, and alternatives to animal studies that still use patient-derived tissues.

Patient-Derived Xenograft and Organoid Models for Precision Medicine Targeting of the Tumour Microenvironment in Head and Neck Cancer

“…Further, the majority of HNSCC PDX tumours are engrafted subcutaneously on the flank of mice, which typically leads to a non-invasive phenotype contrary to the often highly aggressive and invasive behaviour of HNSCC tumours. Orthotopic implantation into the tongue, floor of mouth, or buccal mucosa can promote metastasis, but comes with animal welfare implications with regards to feeding and requirements for non-invasive imaging for tumour size measurements [ 114 ]. Finally, acquisition of copy number alterations (CNA) in subsequent generations of PDX tumours has led to questions about the reliability of PDXs to model the donor tumour [ 115 , 116 ].…”

Animal Models for Radiotherapy Research: All (Animal) Models Are Wrong but Some Are Useful

“…Several papers also focus on recent advances in modelling tumour responses. For example, Cosper et al [ 15 ] review the approaches, biological advantages and potential pitfalls of patient-derived models in head and neck cancer. In a corollary article, Vincent-Chong and Seshadri [ 16 ] present a novel syngeneic mouse model of oral squamous cell carcinoma derived from a chemically-induced tongue tumour in a C57BL/6 mouse.…”

Precision Medicine in Head and Neck Cancers: Genomic and Preclinical Approaches

“…Moreover, the implantation is performed subcutaneously in the mice’s flanks, and not orthotopically, with a consequent decrease of the translational powers of obtained results. On the other hand, orthotopic implantation into oral tissues entails many disadvantages, such as the development of a tumour mass in the oral cavity that prevents the animal from feeding [ 181 ].…”