Current Gene Therapy Strategies for Colorectal Cancer

Rachel      Hargest

doi:10.2174/1389202003351797

Abstract

Colorectal cancer is one of the commonest cancers worldwide and despite improvements in surgery, radiotherapy and chemotherapy the overall five year survival is around 50 percent. Therefore, novel treatments need to be developed in order to add to the therapeutic armamentarium. Gene therapy is a promising new modality of treatment which can be used in combination with existing therapies. Current gene therapy strategies usually involve the use of interventional genetic techniques to enhance the immunological response to a tumour or to deliver cytotoxic agents to tumour cells. Such strategies can be used alone or in combination and are being explored in a number of clinical trials. More recently, attempts to correct some of the underlying genetic abnormalities in various cancers have been made. The genetic changes which lead to the development of colorectal cancer are well described and, therefore, may be amenable to correction. Replacement of tumour suppressor genes such as p53 has been shown to re verse phenotypic changes in animal models and has been licensed for human use in clinical trials. This technique appears to be safe in the small number of patients treated, thus far and several tumour responses have been demonstrated. Prophylactic treatment with tumour suppressor genes for individuals at high risk of developing colorectal cancer, such as those with familial adenomatous polyposis, may prove beneficial in preventing or delaying the onset of malignant change. The search for safer and more efficient gene delivery vectors continues since traditional adenovirus, retrovirus and plasmids are beset by problems of safety or efficiency. The ultimate gene delivery vector is likely to be a human artificial chromosome which would allow delivery of a large number of genes together with their controlling sequences. Colorectal cancer is a disease which can be attacked by a number of genetic mechanisms in order to kill tumour cells directly, prevent further growth and enhance the anti-tumour immune respon se. Clinical protocols need to move from the stage of small clinical trials to mass application and it is likely that improved gene delivery vectors will be necessary in order for this to occur.

Keywords: Gene Therapy, Colorectal Cancer, Cytotoxic agents, Tumor cells, Immunotherapy, Retinoblastoma RB, Tumor, Multiple Drug resistance, Etoposide