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Restoration of the G1 Checkpoint and the Apoptotic Pathway Mediated by Wild-type p53 Sensitizes Squamous Cell Carcinoma of the Head and Neck to Radiotherapy
Esther H. Chang, PhD;
Yng-Ju Jang, MSc;
Zhengmei Hao;
Gloria Murphy, MSc;
Antonina Rait, PhD;
Willard E. Fee, Jr, MD;
Howard H. Sussman, MD;
Patricia Ryan, PhD;
Yawen Chiang, PhD;
Kathleen F. Pirollo, PhD
Arch Otolaryngol Head Neck Surg. 1997;123(5):507-512.
Abstract
Background
A significant number of squamous cell carcinomas of the head and neck (SCCHN) resist radiation treatment, the most common form of adjuvant therapy for this disease. The presence of a mutant form of the tumor suppressor gene p53 has been correlated with disruption of programmed cell death (apoptosis) and reduced cell cycle arrest, resulting in increased radiation resistance and survival.
Methods and Results
We introduced by means of an adenoviral vector a functional p53 gene into a radiation-resistant SCCHN cell line that harbors mutant p53. Replacement of wild-type p53 restored the G1 block and apoptosis in these cells in vitro. Moreover, introduction of wild-type p53 sensitized SCCHN-induced mouse xenografts to radiotherapy in vivo.
Conclusion
The combination of p53 replacement gene therapy with conventional radiotherapy may treat SCCHN more effectively.
Arch Otolaryngol Head Neck Surg. 1997;123:507-512
Author Affiliations
From the Division of Otolaryngology, Department of Surgery (Drs Chang, Jang, Rait, Fee, and Pirollo and Ms Hao), and the Department of Pathology (Ms Murphy and Dr Sussman), Stanford University, Stanford, Calif; and Genetic Therapy Incorporated/Sandoz, Gaithersburg, Md (Drs Ryan and Chiang). Drs Chang, Rait, and Pirollo are now with the Department of Otolaryngology, Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC.
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