Preclinical and clinical experience of antisense therapy for solid tumors.

The mechanisms by which the therapeutic window and clinical utility of antisense drugs can be fully optimized are discussed. Recent preclinical and clinical efforts are focusing on defining and optimizing the combination therapy regimes in which ONs are most efficacious. However, additional research is required to define which, and how, oncogenes interact with each other and the circumstances under which synergistic therapeutic benefit might be achieved using antisense drugs. The therapeutic window of antisense drugs is also being expanded by the use of novel delivery systems, including lipid-based carriers for systemic delivery. Taken together, molecular therapeutics based on antisense technology, coupled with effective delivery systems increasing drug potency, are anticipated to substantially improve the treatment of human neoplasms.