Oral squamous cell carcinoma accounts for 95% of human head and neck squamous cell carcinoma cases. It is highly malignant and aggressive, with a poor prognosis and a 5-year survival rate of <50%. In recent years, basic and clinical studies have been performed on the role of the mitogen-activated protein kinase (MAPK) signaling pathway in oral cancer. The MAPK signaling pathway is activated in over 50% of human oral cancer cases. Herein, we review research progress on the MAPK signaling pathway and its potential therapeutic mechanisms and discuss its molecular targeting to explore its potential as a therapeutic strategy for oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) affects a large number of individuals worldwide. Despite advancements in surgery, radiation, and chemotherapy, satisfactory outcomes have not been achieved. In recent years, the success of drugs targeting programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) has led to breakthroughs in cancer treatment, but systematic summaries on their effectiveness against OSCC are lacking. This article reviews the latest research on the PD-1/PD-L1 pathway and the potential of combination therapy based on this pathway in OSCC. Further, it explores the mechanisms involved in the interaction of this pathway with exosomes and protein-protein interactions, and concludes with potential future OSCC therapeutic strategies.

Residual tumor cells persisting in the surgical bed are the principal drivers of postoperative tumor recurrence, yet the immunosuppressive wound healing microenvironment limits immune activation and compromises antigen enrichment and cross‐presentation. To address this issue, we exploited tumor cell invasiveness to construct isolated niches that confine the cells in micron‐scale chambers shielded from external microenvironmental perturbations. For proof of principle, we fabricated a hyaluronic acid‐based double‐network hydrogel comprising HAMA and PEGDA. Hyaluronidase‐dependent invasive tumor cells degrade the hydrogel to form isolated niches and are physically confined. The hydrogel releases DOX/LDH‐engineered Escherichia coli minicells that accumulate in niches, eradicating trapped tumor cells via high local DOX concentrations. Spatial confinement enriches tumor antigens and excludes normal tissue proteins, improving LDH‐mediated antigen capture. Minicells then deliver antigens to dendritic cells; post‐phagocytosis, LDH releases antigens, and Mn ^{2 +} activates the cGAS‐STING pathway, synergistically boosting immune activation.

Background: The prognosis and survival rate of patients with head and neck squamous cell carcinoma (HNSCC) remain a serious public health concern. Therefore, elucidation of the underlying mechanisms responsible for the biological behavior of HNSCC is crucial for the development of effective treatment strategies. Methods and Materials: In this study, we analyzed TCGA database and found that MAPK12 was overexpressed in tumor samples compared to normal samples, which was confirmed by microarray expression profiles, quantitative real-time polymerase chain reaction, and immunohistochemistry. Results: Cell functional experiments, including the cell counting kit-8 assay, wound healing test, and Transwell assay, revealed that MAPK12 overexpression increased the proliferation, invasion, and migration of HNSCC cells. A correlation was observed between MAPK12 expression and patient survival in HNSCC across several clinicopathological variables, including disease grade and stage. Analysis of immune-related functions demonstrated that HNSCC patients with low MAPK12 expression had a more favorable tumor immune microenvironment and better immunological functions. Conclusion: Collectively, our study identified for the first time that MAPK12 is upregulated in HNSCC, functioning as an oncogene, indicating a suppressive tumor immune microenvironment and poor prognosis since it could promote cancer cell proliferation, invasion, and migration. However, further studies are needed to gain a more comprehensive understanding of the role of MAPK12 in HNSCC and other tumor types.