Abstract
Preclinical cancer research increasingly demands sophisticated models for the development and translation of efficient and safe cancer treatments to clinical practice. In this regard, tumor-grafted chorioallantoic membrane (CAM) models are biological platforms that account for the dynamic roles of the tumor microenvironment and cancer physiopathology, allowing straightforward investigations in agreement to the 3Rs concept (the concept of reduction, refinement, and replacement of animal models). CAM models are the next advanced model for tumor biological explorations as well as for reliable assessment regarding initial efficacy, toxicity, and systemic biokinetics of conventional and emerging neoplasm treatment modalities. Here we report a standardized and optimized protocol for the production and biocharacterization of human papillomavirus (HPV)-negative head and neck chick chorioallantoic membrane models from a commercial cell line (SCC-25). Oral malignancies continue to have severe morbidity with less than 50% long-term survival despite the advancement in the available therapies. Thus, there is a persisting demand for new management approaches to establish more efficient strategies toward their treatment. Remarkably, the inclusion of CAM models in the preclinical research workflow is crucial to ethically foster both the basic and translational oncological research on oral malignancies as well as for the advancement of efficient cancer treatment approaches.
Highlights
Preclinical cancer research increasingly demands sophisticated models for the development and translation of efficient and safe cancer treatments to clinical practice
Despite some difficulties in the application of chorioallantoic membrane (CAM) models to long-term investigations, their highly vascularized membrane together with the immature immune response allowed the low rejection rate grafting of several tissues and the study of various neoplasms, including osteosarcoma, glioblastoma, pancreatic carcinoma, and colon carcinoma.[20−23] Several variable tumor engraftment methods for CAM model production have been reported, yet these studies focus on the tumor biology or the evaluation of a treatment avoiding reporting a standard protocol for the production of the models.[24,25]
In order to address this demand, we report a standardized protocol for the composition as well as the cascade assays for the characterization of a commercial human papillomavirus (HPV)-negative head and neck cell line (SCC-25) grafted on chick chorioallantoic membrane of fertilized Leghorn chicken eggs
Summary
Preclinical cancer research increasingly demands sophisticated models for the development and translation of efficient and safe cancer treatments to clinical practice. Article disease are significant factors determinant of mortality.[8] oral malignancies, including tongue cancer, continue to have severe morbidity with less than 50% longterm survival despite the advancement in the available and emerging therapies.[4,5,9,10] In this regard, understanding the biological processes at the basis of oral malignancies and the development of new therapeutic strategies to improve the survival rate of patients while preserving the structure and function of the involved organs are crucial topics for their management.[11] In this context, in vivo models are pivotal to foster the advancements in oncology by bridging the gap between preclinical investigations and human clinical trial on conventional and emerging therapeutic approaches as well as to understand tumor cell behaviors in a physiological environment.[19] The most widely employed in vivo models are murine, and they have been crucial to establish most of the current models in pediatric oncology and to develop some drugs, among which topotecan and irinotecan.[7] murine models are relevant for absorption− distribution−metabolism−excretion−toxicity (ADMET) investigations.[12−14] genetically immunocompromised murine models have very high costs of maintenance, and the tumor engraftment may require up to 4 months.
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