Preclinical in vitro models of HNSCC and their role in drug discovery - an emphasis on the cancer microenvironment and microbiota.

Introduction: Head and neck squamous cell carcinoma (HNSCC) is the seventh most common cancer worldwide. Treatment options and patient outcomes have not improved significantly over the past decades, increasing the need for better preclinical models. Holistic approaches that include an intact and functional immune compartment along with the patient's individual tumor microbiome will help improve the predictive value of novel drug efficacy.

Areas covered: In this review, we describe the challenges of modeling the complex and heterogeneous tumor landscape in HNSCC and the importance of sophisticated patient-specific 3D in vitro models to pave the way for clinical trials with novel immunomodulatory drugs. We also discuss the impact of the tumor microbiome and the potential implications for prospective drug screening and validation trials.

Expert opinion: The repertoire of well-characterized preclinical 3D in vitro models continues to grow. With the increasing attention to the complex cellular, immunological, molecular, and spatio-temporal characteristics of tumors, well-designed proof-of-concept studies to test novel drug efficacy are on the verge of providing valuable, practice-changing insights for clinical trials. Bringing together expertise and improving collaboration between clinicians, academics, and regulatory agencies will facilitate the translation of preclinical findings into clinically meaningful outcomes.