Unravelling molecular mechanism of oral squamous cell carcinoma and genetic landscape: an insight into disease complexity, available therapies, and future considerations

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.

Keywords: genetic predisposition; immunotherapy; molecular pathways; oral squamous cell carcinoma (OSCC); therapeutic challenges.

Figure 1

Negative and positive (Protective) factors associated with oral squamous cell carcinoma.

Figure 2

Illustration of the molecular pathways implicated in cancer initiation and progression. The microbiome and other signals influence receptor tyrosine kinase (RTK) signaling, leading to the activation of EGFR, HER2/EGFR, and MET, which in turn trigger downstream pathways such as JAK-STAT, RAS-RAF-MEK-ERK, PI3-K-Akt, and Wnt/β-catenin signaling. These pathways promote cell survival, proliferation, and cell cycle progression, contributing to tumorigenesis. Additionally, a combinational treatment approach incorporating beneficial bacteria, immune checkpoint inhibitors (such as anti-PD-1), and cancer vaccines may help transform an immunosuppressive or “cold” tumor into an immune-active or “hot” tumor. This transformation is characterized by enhanced infiltration of cytotoxic T lymphocytes (CTLs), natural killer (NK) cells, dendritic cells (DCs), and M1 macrophages, ultimately fostering a more effective anti-tumor immune response.