Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

The specific and rational targeting of key genes, identified to be vital to driving cancer growth, has recently led to the successful development of several small molecule and antibody therapeutics. However, despite considerable efforts, antisense oligonucleotides (ASO) have yet to prove their worth as targeted therapies. However, many important genes cannot be readily targeted by antibodies or small molecules, and could be blocked by ASOs. Moreover, the latest generation of ASOs is safe, well tolerated and able to modulate target protein expression both in surrogate and tumour tissue in the clinic. This review will describe the experience acquired with these agents to date and will raise critical issues relevant to the further optimal development of these agents. Future clinical studies need to evaluate combinations of several different ASO targeting multiple key targets, including strategies that reverse functional redundancy of the key target (e.g., targeting several Bcl family members including Bcl-2 and Bcl-x). Approaches to maximise the duration of target blockade yet avert the need for prolonged intravenous infusions, with the consequent risk of line infection and thrombosis, are also needed. These may include slow-release depot subcutaneous formulations. Short interfering (Si) RNA therapeutics, which are now being evaluated in early clinical trials, are also envisioned to impact the future utility of this class of therapeutics. The high manufacture cost of these agents, when compared with small chemical molecules, could however, limit their success unless cost-effective manufacturing processes are developed.

Original publication

DOI

10.1016/j.ejca.2005.06.029

Type

Journal article

Journal

Eur J Cancer

Publication Date

12/2005

Volume

41

Pages

2812 - 2818

Keywords

Clinical Trials as Topic, Genetic Therapy, Humans, Neoplasm Proteins, Neoplasms, Oligonucleotides, Antisense, RNA, Neoplasm