Presentation description

Head and neck squamous cell carcinomas (HNSCCs) pose a significant global health challenge, with approximately 890,000 new diagnoses and 450,000 associated deaths reported each year. Treatments include surgery, radiotherapy, chemotherapy, and adjuvant immunotherapy. Despite recent therapeutic advancements, over 65% of patients with HNSCCs have metastatic and/or recurrent disease. Heparin, clinically employed as an anti-coagulant, has shown promising anti-tumor properties by disrupting the CXCL12/CXCR4 signaling axis, implicated in tumor survival, proliferation, invasion, and in chemoradiation resistance and cancer recurrence. The CXCL12/CXCR4 signaling axis has recently been identified as a new target in HNSCC. Although promising, the short half-life and anti-coagulant activity of heparin raise concerns about its safety and clinical utility in treating HNSCCs. This project aims to develop and evaluate synthetic heparin-like glycosaminoglycans that effectively modulate pro-tumor processes through CXCL12/CXCR4 pathway inhibition with minimal anti-coagulant activity, as a novel adjuvant therapeutic strategy for treating advanced and metastatic HNSCCs. Compounds were synthesized by crosslinking and sulfating hyaluronic acid (HA). Synthesized compounds were then characterized using proton nuclear magnetic resonance and Fourier transform infrared spectroscopy. Subsequently, the compounds were assessed for CXCL12 binding affinity using a sandwich immunoassay and evaluated for anti-coagulant activity in prothrombin and activated partial thromboplastin blood coagulation tests. Results indicate that the compounds were successfully crosslinked and sulfated, bound to CXCL12 with high affinity compared to heparin and HA, and exhibited negligible anti-coagulant activity compared to heparin. These findings suggest that synthetic glycosaminoglycans show great promise for further therapeutic evaluation as adjuvant cancer therapies for HNSCCs.