Ex Vivo Culture Models to Indicate Therapy Response in Head and Neck Squamous Cell Carcinoma

Abstract

Head and neck squamous cell carcinoma (HNSCC) is characterized by a poor 5 year survival and varying response rates to both standard-of-care and new treatments. Despite advances in medicine and treatment methods, mortality rates have hardly decreased in recent decades. Reliable patient-derived tumor models offer the chance to predict therapy response in a personalized setting, thereby improving treatment efficacy by identifying the most appropriate treatment regimen for each patient. Furthermore, ex vivo tumor models enable testing of novel therapies before introduction in clinical practice. A literature search was performed to identify relevant literature describing three-dimensional ex vivo culture models of HNSCC to examine sensitivity to chemotherapy, radiotherapy, immunotherapy and targeted therapy. We provide a comprehensive overview of the currently used three-dimensional ex vivo culture models for HNSCC with their advantages and limitations, including culture success percentage and comparison to the original tumor. Furthermore, we evaluate the potential of these models to predict patient therapy response.

Keywords: 3D cell culture; drug response; ex vivo model; head and neck cancer; histoculture; organoid; personalized therapy; preclinical prediction model; primary cell culture; sensitivity testing.

Figure 1

Flow diagram of the systematic literature search performed.

Figure 2

Processing of the primary tumor sample into tumor fragments by mechanical modification and subsequently into a single-cell suspension by enzymatic dissociation.

Figure 3

Primary cell culture techniques divided into two-dimensional and three-dimensional models. (A) 2D monolayer from single-cell suspension; (B) micro(fluidic) device; (C) spheroids in suspension culture; (D) spheroids embedded in a scaffold-based system; (E) spheroids in an agitation-based system, e.g., a spinner flask; (F) spheroids in hanging-drop cultures; (G) spheroids formed by magnetic levitation; (H) histoculture in culture insert; (I) patient-derived xenograft mouse model with subcutaneous injection. Image of xenograft was modified from Servier Medical Art (http://smart.servier.com/), licensed under a Creative Common Attribution 3.0 Unported License (https://creativecommons.org/licences/by/3.0/).

Figure 4

Principles of sphere formation from primary tumor cells. (A) Sphere formed by aggregation of multiple cells in a single-cell suspension; (B) sphere formed by clonal expansion of a single cell with proliferating potential; (C) sphere formed by clonal expansion and lineage-dependent differentiation of a single cell with proliferating potential.