Exploring cell death pathways in oral cancer: mechanisms, therapeutic strategies, and future perspectives.

Abstract

Oral squamous cell carcinoma (OSCC) represents a significant global health challenge, characterized by aggressive progression and poor therapeutic response despite advances in treatment modalities. This review provides a comprehensive analysis of diverse cell death mechanisms in OSCC, encompassing traditional pathways (apoptosis, autophagy, and necrosis), newly characterized mechanisms (ferroptosis, pyroptosis, and necroptosis), and emerging pathways (cuproptosis, anoikis, parthanatos, and entosis). By examining the molecular basis of these pathways, particularly the crucial roles of p53 signaling and miRNA regulation, we highlight how their dysregulation contributes to treatment resistance and tumor progression. The review synthesizes recent evidence demonstrating the complex interplay between these ten distinct cell death mechanisms and their impact on the tumor microenvironment and immune response. We evaluate innovative therapeutic approaches that target these pathways, including novel small molecules, combination strategies, and immunomodulatory treatments that exploit specific cell death mechanisms to enhance therapeutic efficacy. Special attention is given to emerging personalized medicine strategies that consider individual tumor characteristics and cell death pathway profiles. By integrating current challenges with future research directions, this review provides a framework for developing more effective treatments that can leverage multiple cell death pathways to overcome therapy resistance and improve outcomes for oral cancer patients.