Saltar al contenido
Merck

Radiosensitization approaches for HPV-positive and HPV-negative head and neck squamous carcinomas.

International journal of cancer (2019-07-10)
Rüveyda Dok, Marieke Bamps, Mary Glorieux, Peihua Zhao, Anna Sablina, Sandra Nuyts
RESUMEN

Radiotherapy is one of the most used treatment approaches for head and neck squamous cell carcinoma (HNSCC). Targeted inhibition of DNA repair machinery has the potential to improve treatment response by tailoring treatment to cancer cells lacking specific DNA repair pathways. Human papillomavirus (HPV)-negative and HPV-positive HNSCCs respond differently to radiotherapy treatment, suggesting that different approaches of DNA repair inhibition should be employed for these HNSCC groups. Here, we searched for optimal radiosensitization approaches for HPV-positive and HPV-negative HNSCCs by performing a targeted CRISPR-Cas9 screen. We found that inhibition of base excision repair resulted in a better radiotherapy response in HPV-positive HNSCC, which is correlated with upregulation of genes involved in base excision repair. In contrast, inhibition of nonhomologous end-joining and mismatch repair showed strong effects in both HNSCC groups. We validated the screen results by combining radiotherapy with targeted inhibition of DNA repair in several preclinical models including primary and recurrent patient-derived HNSCC xenografts. These findings underline the importance of stratifying HNSCC patients for combination treatments.

MATERIALES
Referencia del producto
Marca
Descripción del producto

Sigma-Aldrich
Anti-LIG1 antibody produced in rabbit, affinity isolated antibody