Targeting PLK1 with Onvansertib and Radiation in Head and Neck Cancer

Radiotherapy is a key treatment for head and neck squamous cell carcinoma (HNSCC) especially in patients with human papilloma virus-negative (HPV-) HNSCC. Our studies identify polo-like kinase 1 (PLK1) as a promising target for HNSCC. PLK1 inhibition with onvansertib reduces cell viability and spheroid growth of HPV- HNSCC cells. PLK1 inhibition combined with radiation increases G2/M arrest, decreases colony formation of HPV- HNSCC cells, and reduces tumor growth in vivo. RNA-sequencing demonstrates radiation increases MMP10 expression but PLK1 inhibition reverses this effect in HPV- HNSCC cells. PLK1 inhibition also reduces MMP10 activity in HPV- HNSCC cells. These findings suggest that combining PLK1 inhibition with radiation may improve therapeutic response for HPV- HNSCC via MMP10, offering a novel approach to overcome radiation resistance.