Journal of Taibah University Medical Sciences · Oct 12, 2026
Impact of aging on the tumor microenvironment in oral cancer: Mechanisms and therapeutic perspectives
By Prasad P, Amer A, Shamsi A et al.
ABSTRACT: Oral cancer is a major global health problem, and its impact is particularly pronounced in older adults. The aging process markedly affects the tumor microenvironment, influencing tumor initiation, progression, and response to treatment. This review examines the available evidence on the effects of aging on the tumor microenvironment in oral cancer, the progression of oral diseases, and the implications for treatment. Studies were collected through a systematic search of the literature published in the PubMed and MEDLINE databases from January 2010 to January 2025. Several age-related changes, such as cellular senescence, immunosenescence, extracellular matrix remodeling, chronic low-grade inflammation associated with aging, and vascular dysfunction, contribute to creating an environment conducive to tumor growth, facilitating immune evasion and increasing treatment resistance. This review discusses the mechanisms of cellular senescence, immune dysregulation, oxidative stress, and endothelial dysfunction, as well as their roles in impairing antitumor immunity and reducing treatment response in older patients. Research indicates that these age-related changes are interconnected and act together to promote tumor progression and contribute to treatment resistance. Research in aging biology and the tumor microenvironment has helped highlight new therapeutic approaches that may include targeting mechanisms of cellular senescence, modulating the immune response, and targeting vascular aging. A deeper understanding of age-related changes in the tumor microenvironment is still needed to develop tailored therapeutic interventions that account for aging, thereby contributing to improved clinical outcomes in older adults with oral cancer.