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. Overall design: RNA-seq profiling of human head and neck squamous cell carcinoma (HNSCC) cell lines (HN5, UMSCC47) treated with the PLK1 inhibitor onvansertib in combination with radition. HNSCC cells were treated with vehicle, onvansertib alone, radiation alone, and onvasertib combined with radiation (n = 3). HNSCC cells were treated with onvansertib for 24 hours then irradiated (4 Gy), and RNA was collected 24 hours later.