Section Review Oncologic, Endocrine & Metabolic: Gene therapy for cancer therapeutics

Abstract

This review highlights current strategies and significant developments being employed in gene therapy for neoplastic diseases. Three main approaches, mutation compensation, molecular chemotherapy and genetic immunopotentiation, have been undertaken. Mutation compensation relies on strategies to ablate activated oncogenes at the level of DNA (triplex), messenger RNA (antisense or ribozyme) or protein (intracellular single chain antibodies), and augment tumour suppressor gene expression. Molecular chemotherapy uses the delivery of a toxin gene to tumour cells for eradication. This can be accomplished by either transductional targeting, whereby the toxin is specifically delivered to the tumour, or by transcriptional targeting, whereby tumour-specific transcriptional activators are employed selectively to ‘turn on’ the toxin gene exclusively within the tumour. Genetic immunopotentiation refers to treatment based on the induction of a specific immune response against tumour-associated antigens (TAAs). The main objective of this therapy is to reinforce and bolster the immune system of the cancer-bearing host, resulting in rejection of the tumour.

Key Words:

• antisense
• cancer
• gene therapy
• infiltrate lymphocytes
• intracellular single chain antibodies
• ribozyme
• transcriptional transductional targeting
• triplex
• tumour-polynucleotide immunisation