AUTHOR=Shebbo Salima , Alateyah Nooralhuda , Yassin Esraa , Mahmoud Doaa El Sayed , Tamimi Faleh , Anweigi Lamyia , Elhissi Abdelbary , Abou-Saleh Haissam , Elrayess Mohamed A. , Agouni Abdelali TITLE=Unravelling molecular mechanism of oral squamous cell carcinoma and genetic landscape: an insight into disease complexity, available therapies, and future considerations JOURNAL=Frontiers in Immunology VOLUME=Volume 16 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1626243 DOI=10.3389/fimmu.2025.1626243 ISSN=1664-3224 ABSTRACT=Oral squamous cell carcinoma (OSCC) is a heterogeneous malignant neoplasm characterized by intricate molecular pathways and a varied genetic landscape, resulting in a diminished 5-year survival rate. Due to this complexity, many trials of emerging therapies are failing to improve the outcome and survival rate of OSCC, posing a great challenge in the management of this cancer. This review examines the key molecular pathways, genetic susceptibility, and the influence of the microbiome in the advancement of OSCC. Furthermore, it analyses contemporary therapeutic approaches, their limitations, and prospects, especially the incorporation of immunotherapy. The discussion will also encompass the difficulties in turning research findings into successful therapeutic applications and enhancing the patient’s quality of life.