Gene therapy principles and strategies for head and neck cancer.
The ongoing preclinical and now human clinical investigation of gene therapy in head and neck cancer and cancer and cancer overall have provided a few foundation points of information. The first point is that viral and nonviral gene therapy has demonstrated efficacy in a variety of animal models and these successes support consideration and evaluation of gene therapy in human clinical trials. Regarding the retrovirus as a vehicle for gene transfer in humans, it appears to be a safe vehicle. There has been no significant short- or long-term toxicity associated with a wide application of retroviral gene therapy in human patients [12]. Regarding adenovirus as a vehicle, there are less numbers and less advanced trials, but the associated toxicities reported thus far have been both transient and relatively minor. Nonviral cationic lipid-mediated gene transfer also appears safe in human patients. These points are significant because they establish the safety foundation for delivering potentially therapeutic genes to humans. Without this safety data, gene therapy would not have a future in the treatment of cancer. At the present Phase I stage of human clinical trial investigation for head and neck cancer, the focus remains on patients with advanced or recurrent incurable cancer. Although this patient population is a standard choice for establishing the safety of novel therapies, the greatest chance of eventual success with currently available gene transfer vehicles and gene therapy strategies will most likely be in those patients with less advanced stages of disease. Another future potential for gene therapy in head and neck cancer may be in combination with surgery or radiation or chemotherapy. At some acceptable ratio of efficacy to toxicity, gene therapy may also prove effective against earlier stage cancer either as a primary or adjuvant therapy. In conjunction with the evolution of molecular diagnostics, gene therapy strategies may provide the means for preventing the malignant progression of premalignant head and neck lesions upon early diagnosis.
O'Malley
B W
BW
Department of Otolaryngology, Head and Neck Surgery, Johns Hopkins University, Baltimore, Md., USA. bomalley@smail.umaryland.edu
Couch
M E
ME
D016207:Cytokines / Q000235:genetics*; D018014:Gene Transfer Techniques; D016147:Genes, Tumor Suppressor; D015316:Genetic Therapy; D005822:Genetic Vectors; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000628:therapy*; D006801:Humans
D016207:Cytokines