Revolutionizing precision medicine in oral squamous cell carcinoma: Harnessing 3D in vitro models for translation

Oral squamous cell carcinoma (OSCC) is a highly aggressive neoplasm of the surface epithelium that arises from the mucosal lining of the mouth. The poor prognosis can be attributed to the complex tumor microenvironment (TME) in OSCC, which is crucial for tumor progression, angiogenesis, invasion, metastasis, and therapeutic resistance. In recent years, three-dimensional (3D) in vitro models have emerged as powerful tools to study OSCC biology and evaluate targeted therapies in a more physiologically relevant context. Advanced models such as tumor spheroids, patient organoids and microfluidic devices offer unique possibilities to reconstitute intricate cellular interactions, ECM dynamics as well as physiological gradients found in the OSCC TME. The 3D OSCC model provides powerful preclinical tools for drug screening and mechanistic studies of this devastating malignancy. In this review, we discuss the role of the tumor-immune microenvironment (TIME) in tumorigenesis and the 3D in vitro cultures in recreating the tumor microenvironment paving the way for the development of personalized medicine in OSCC.