Antisense therapy for lymphomas.

Abstract

The potential ability of antisense oligonucleotides to downregulate the expression of oncogenes involved in lymphoma, with minimal toxicity can be achieved. The possibility of combining antisense therapy such as BCL-2 antisense with chemotherapy will probably provide an interesting means of overcoming tumour cell resistance to chemotherapy in lymphoma and a range of other high BCL-2 expressing malignancies. As additional antisense molecules targeting oncogenes involved in lymphomas become available, it will be possible to combine them with AO to enhance their efficacy, either targeting the same gene at two sites or more a combination of genes (for example, BCL-2 and MYC in Burkitt's lymphoma). Of major importance are approaches to improve AO uptake into cells which is currently poor. Methods to improve antisense uptake into the cell are required and in addition a new generation of oligonucleotides free of the nonspecific thioate toxicities are required. AO are a dramatic new area of research and as such require much evaluation if they are to be applied maximally. Both in vitro and in vivo efficacy has been established. With care, novel therapies based on the biology of the malignant cell may be determined on a scientific basis and may help improve the treatment of patients with these diseases. Gene silencing by antisense oligonucleotides has a role to play as demonstrated in lymphomas.