Squamous Cell Carcinoma of Head and Neck

Cetuximab, a chimeric IgG1 monoclonal antibody anti-EGFR, is the only EGFR-targeted agent approved for HNSCC and has shown efficacy in both locally advanced (in platinum-unfit patients) and recurrent/metastatic (R/M) settings...Irreversible pan-HER tyrosine kinase inhibitors (e.g., afatinib, dacomitinib), dual-target bispecific antibodies such as duligotuzumab (EGFR/HER3), petosemtamab (EGFR/LGR5) or ficerafusp alfa (EGFR/TGF-β) have led to promising preclinical and early-phase clinical activity...While EGFR remains a valid therapeutic target, future efforts must focus on biomarker-driven patient selection and combination strategies to enhance efficacy and durability of response. Ongoing trials will further define the role of emerging anti-EGFR agents and their integration into HNSCC treatment algorithms.

Based on the study findings, an increase antigen-specific immune response by vaccinating the patient with a tumor-associated peptide in combination with anti-PD-1 antibody would be advantageous in HNSCC. Efforts into finding and developing new combination therapies should be further advanced.

P1, N=75, Suspended, Dana-Farber Cancer Institute | Trial completion date: Jan 2026 --> Jan 2027 | Recruiting --> Suspended | Trial primary completion date: Dec 2025 --> Dec 2026

P=N/A, N=100, Active, not recruiting, Royal Marsden NHS Foundation Trust | Trial completion date: Dec 2028 --> Dec 2030 | Trial primary completion date: Dec 2027 --> Dec 2029

P1/2, N=230, Recruiting, Exscientia AI Ltd., a wholly owned subsidiary of Recursion Pharmaceuticals, Inc. | N=165 --> 230

Emerging bulk, single-cell and spatial multi-omics studies support the idea that pathway activity is compartmentalized rather than uniform, providing a mechanistic rationale for the limited performance of first-generation IDO1 inhibitor strategies in unselected clinical settings. This mini-review synthesizes current evidence on Trp-Kyn microdomains in the HNSCC TME and discusses therapeutic opportunities that move beyond single-enzyme inhibition, including dual IDO1/TDO2 targeting, AhR antagonism and biomarker-guided combination regimens to restore antitumor immunity.

The identification and validation of biomarkers reflecting this continuum could enable the establishment of molecular margins-improving risk assessment, reducing local recurrence, and advancing personalized oncologic surgery in HNSCC. Standardizing definitions and sampling protocols for "normal adjacent tissue" remains essential for future translational research.

In conclusion, HESP amplifies CSP-induced apoptosis in Hep-2 cells through TRPM2-dependent oxidative stress, Ca2+ dysregulation, and mitochondrial dysfunction. These findings identify TRPM2 as a mechanistic mediator of HESP-enhanced chemosensitivity in LSCC.

Future research should prioritize paired tumor-node lncRNA profiling, validation of FNAB-based molecular assays, and integration of multi-omics data for predictive modeling. Overall, integrating lncRNA analysis into ultrasound-guided fine-needle aspiration biopsy may enhance the detection of occult nodal metastases in head and neck squamous cell carcinoma and support more accurate nodal staging in clinically node-negative patients.

P1, N=1314, Recruiting, Exelixis | Active, not recruiting --> Recruiting

P=N/A, N=50, Active, not recruiting, Yonsei University | Trial completion date: Feb 2023 --> Sep 2026 | Trial primary completion date: Dec 2022 --> Sep 2026

P2, N=30, Not yet recruiting, University Health Network, Toronto