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 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.

In-vitro and in-vivo models for the identification and validation of radioprotectors and radiosensitizers

“…For a long time, zebrafish and their embryos have been used to develop xenograft models using established cancer cell lines or combining the tumor and stromal tissues together, which helps to study rapid drug screening [36]. The Zebrafish model helps in the assessment of radioprotector and radiosensitizer from various analyses [10].…”

“…Experiments involving organoids to model tumor xenografts need a repeated collection of tumor tissues or require a replenishable source of tissues for experimental replicates or large-scale culture in the form of organoids. However, this problem can be addressed with PDOs, which are derived from PDXs generated in animal models thus, repeated patient biopsy and tumor tissue collection will not be required [10].…”

A novel 3D pillar/well array platform using patient-derived head and neck tumor to predict the individual radioresponse

“…Several studies have suggested various biomarkers to correlate with tumor radioresponse, i.e., multiple omics data, ultrasound radiomics, gene signatures, and clinicopathological predictors [6] , [7] , [8] , [9] . Patient-derived culture (PDC) models (xenograft models, organoid models, or humanized mice models) recently have been shown to recapitulate the biological and genetic heterogeneity of patient-native tumors, offering a useful platform to test an individual tumor response to chemotherapeutic agents or irradiation [10] . Also, with the advancement of bioengineering techniques and microfluidics, the 3D culture method of PDCs has the advantages of being easily reproducible and applicable to a high-throughput platform while maintaining the diversity of patient-native cancer tissues [ 11 , 12 ].…”

Presence of complete murine viral genome sequences in patient-derived xenografts

“…Preclinical evaluation of the effects of potential treatments using in vivo and in vitro platforms is essential for developing successful cancer treatments. As an important in vivo platform, Patient-derived xenograft (PDX) models are developed by implanting human tumor tissues in immune-deficient mice and have been considered a more faithful representation of the in vivo microenvironment for tumor growth 1 – 3 than cell culture. As of July 2020, over 4031 PDX models were deposited in the PDX finder 4 , and at least 19,242 publications related to mouse models of cancer are deposited in the Mouse Tumor Biology Database 5 .…”