Senescence and oral cancer: From mechanisms to therapeutic opportunities

Cellular senescence, characterized by stable cell cycle arrest, plays a multifaceted role in the development of oral cancer, attracting growing attention for its influence on cancer progression and therapeutic approaches. The accumulation of senescent cells in the oral microenvironment, especially with aging, may contribute to intrinsic vulnerability to oral cancer. This review examines the mechanisms connecting senescence to oral cancer, with a focus on DNA damage, inflammation, and epigenetic alterations. Additionally, we discuss emerging therapeutic approaches targeting senescent cells, including senolytics, senomorphics, and immune-based strategies, along with their potential translational applications in oral cancer therapy. Given the complex interplay between senescent cells and the tumor microenvironment, these therapeutic translational strategies hold promise for enhancing patient outcomes. • Senescence has dual roles in oral cancer: tumor promotion and suppression via microenvironmental remodeling. • New senotherapeutics show promise in clearing therapy-induced senescent cells in oral cancer. • Combining senescence-inducing therapies with senotherapeutics offers a new strategy for treating oral cancer.