P53 MEDIATED SENSITIZATION OF SQUAMOUS-CELL CARCINOMA OF THE HEAD ANDNECK TO RADIOTHERAPY

Radiation resistant squamous cell carcinoma of the head and neck cell line JSQ-3 carries a mutant form of tumor suppressor gene p53. Treatme nt of these cells with an adenoviral vector containing wild-type p53 ( Av1p53) was able to inhibit their growth in vitro and in vivo while ha ving no effect on normal cells. More significantly, introduction of wt p53 also reduced the radiation-resistance level of this cell line in v itro, in a viral dose-dependent manner, Furthermore, this radiosensiti zation also carried over to the in vivo situation where the response o f JSQ-3 cell-induced mouse xenografts to radiotherapy was markedly enh anced after treatment with Av1p53, Complete, long-term regression of t he tumors for up to 162 days was observed when a single dose of Av1p53 was administered in combination with ionizing radiation, demonstratin g the effectiveness of this combination of gene therapy and convention al radiotherapy, This sensitization of tumors to radiation therapy by replacement of wtp53 could significantly decrease the rate of recurren ce after radiation treatment. Since radiation is one of the most preva lent forms of adjunctive therapy for a variety of cancers, these resul ts have great relevance in moving toward an improved cancer therapy.