Advanced head and neck cancer treatment: A basic step forward

Patients with advanced head and neck cancer are treated with a combination of chemotherapy (CT), radiotherapy (RT) and surgery. Despite these multimodal treatments, the prognosis of these patients is relatively poor due high local recurrence rates or development of a second primary tumor. The combination of CT (cisplatin, cetuximab) with concurrent RT (CRT) has resulted in minor survival benefits, but with substantial increase in toxicities (causing side effects), when compared to RT alone. This underscores the urgent need for novel radiosensitizers specifically targeting cancer cells and not normal tissues. Ideally, this will lead to improved survival with lower toxicities (side effects). To identify such radiosensitizers, we performed multiple drug screens in absence and presence of irradiation. One screen identified GSK635416A. This drug radiosensitizes cancer cells, thereby outperforming the radiosensitization of cisplatin and cetuximab, while exhibiting virtually no cytotoxicity in the absence of irradiation and in normal fibroblast cells. Screening the FDA-approved oncology drugs library identified rapamycin, raloxifene and tamoxifen as promising radiosensitizers for head and neck cancer.
Another drawback in patients with advanced head and neck cancer is the variability in individual response to CRT. To this aim, we studied the sponge-supported culture assay for culturing fresh tumor biopsies, and optimized this culture method for its potential use as an individual preclinical treatment prediction model.