Targeting radiation resistance of Head and Neck Squamous Cell Carcinoma

Head and Neck Squamous Cell Carcinoma (HNSCC) is a common cause of cancer death. Despite technological advances in radiotherapy, overall survival rate has only improved marginally over the last 30 years. The goal of this study is to search for novel markers to predict radiation response of HNSCC patients and develop novel approaches for HNSCC radiosensitization. We previously found that suppression of protein phosphatase 2A (PP2A) activity leads to impaired DNA repair response. On the other hand, our recent study revealed that 8p loss-of-heterozygosity, which is observed in about 60% of HNSCC patients, leads to radiotherapy resistance that could be partially explained by PP2A down-regulation. As PP2A represents a large family of serine-threonine phosphatases, we plan to identify inhibition of which specific PP2A complexes could trigger radiosensitization of HNSCC and elucidate the mechanisms of the radiosensitization using mass spectrometry-based and biochemical approaches. As the second strategy, we will identify synthetic lethality targets for radiosensitization of oral epithelial cells harboring HNSCC-specific chromosomal deletions or PP2A alterations. We will next validate the identified targets using HNSCC patient-derived xenograft models. The proposed studies will be translated into novel therapeutic approaches for HNSCC patients.

Keywords:radioresistance, predcitive biomarkers, hoofd-hals tumoren, Protein Phosphatase 2A (PP2A)

Disciplines:Laboratory medicine, Palliative care and end-of-life care, Regenerative medicine, Other basic sciences, Other health sciences, Nursing, Other paramedical sciences, Other translational sciences, Other medical and health sciences