10 - Enhancing drug effectiveness by gene transfer

Summary

Introduction

Despite the development of sophisticated chemotherapy regimens together with new surgical and radiotherapy techniques, little headway has been made in the treatment of patients with common types of cancer. Indeed the overall cancer mortality in the population in the Western world is increasing due to a combination of its increasing age distribution and failure of therapeutic impact (Price and Sikora, 1995). Whilst advances in the local control of cancer will continue, these are unlikely to have a major effect on survival, which depends on our ability to control the growth of metastatic disease. Indeed the benefits of adjuvant chemotherapy in breast, colon and several childhood cancers indicate the need for more effective systemic approaches to cancer (Patel and Loprinzi, 1991). Current chemotherapy has a low therapeutic ratio, leading to significant toxicity, poor quality of life and in some programs, a significant mortality. Furthermore tumor cells have the capacity to evolve sophisticated genetic and biochemical mechanisms to overcome the toxic effects of administered drugs. For many types of cancer – breast, ovary, small cell lung and certain types of non-Hodgkin's lymphoma – the initial complete response rate is high but the majority of patients will die of drug resistant metastases within two years of their response (Thames Cancer Registry, 1994). The effects of chemotherapy can be classified into three groups – tumors in which a high complete response and high cure rate is obtained; those with a low response and cure rate and a group where tumor shrinkage is frequent but patients rapidly relapse with drug resistant disease.