The prognosis of patients with some kinds of cancers whose patients are often found unresectable upon diagnosis is still dismal. In these fields, development of a new therapeutic modality is needed and gene therapy represents one promising strategy. So far, numerous cancer gene therapy clinical trials based on these principles have been carried out and have shown the safety of such modalities, but have fallen short of the initial expectations to cure cancers. In this review, we would like to make a problem-oriented discussion of current status of cancer gene therapy research by using mainly gastrointestinal cancers as an example. In order to overcome obstacles for full realization of cancer gene therapy, numerous researches have been conducted by many researchers. Various cancer-selective and non-selective genes, as well as lytic viruses themselves have been employed for gene therapy. In the context of gene delivery method, different kinds of viral and non-viral strategies have been utilized. In addition, surrogate assays, such as soluble markers and imaging, have been developed for safer and more informative clinical trials. Many experiments and clinical trials to date have figured out current obstacles for the realization of an effective cancer gene therapy modality. Tireless efforts to overcome such hurdles and continuous infusion of novel concepts into this field should lead to break through technologies and the cure of the patients.
Cancer gene therapy clinical trials: lessons for the future