Translationally-Relevant Tumor Resection Model for Murine Preclinical Models of Oral Squamous Cell Carcinoma.

Abstract

Currently, the first-line treatment for the most common form of head and neck squamous cell carcinoma (HNSCC), oral cavity squamous cell carcinoma (OSCC), is surgical resection, followed by risk-adapted treatments, such as chemoradiotherapy. However, with the current standard of care and even the emergence of new treatments, such as checkpoint blockade, the overall survival for advanced, recurrent disease remains high, and the prevalence of head and neck cancer is projected to continue to increase in the coming years. Thus, deeper investigation into current standard-of-care modalities, in addition to novel therapeutics, is necessary to translate potential and promising treatment options to patients with HNSCC. Preclinical models are utilized to evaluate the safety and efficacy of potential treatment interventions. Unfortunately, current preclinical models fail to fully embody the surgical procedure many patients receive, as they primarily involve non-surgical treatment modalities, like radiation, chemotherapy, or immunotherapy. Furthermore, existing surgical models are limited by additional reagents needed to support the establishment of tumors in orthotopic sites and the requirement of microsurgery for tumor removal. This warrants the generation of improved and simplified preclinical models to investigate therapeutics and gain insight into locoregional tumor recurrence and treatment resistance. This article describes a novel syngeneic clinically relevant orthotopic murine subtotal resection model that recapitulates the standard of care in OSCC. This model simplifies existing models and results in measurable recurrence following surgical resection of buccal mucosal tumors. Use of this model may lead to valuable insights into tumor recurrence and treatment resistance in patients with OSCC. The establishment of this preclinical model paves the way for further work to investigate how OSCC responds to post-resection adjuvant therapies, capturing the tumor state at the clinically relevant window at which patients generally begin such subsequent treatments.