Antisense Oligonucleotides and Their Anticancer Activities

Abstract

Available cancer therapies still have only limited success against most solid cancer types and inevitably result in the development of multidrug-resistant tumors. There is an urgent need for therapeutic alternatives aiming at compounds with better tolerability at efficacious doses that are directed at defined, disease-relevant molecular targets. The progress made in understanding the molecular basis of mammalian cell transformation has led to the unifying concept of growth regulation and its disorders in cancer cells. It is now well recognized that many products of “cancer genes” encode for proteins that regulate normal mitogenesis and apoptosis. Taken together, these indicate that the carcinogenic process may be viewed as a progressive disorder of signal transduction (Croce 1987;Alitalo et al. 1988;Bos 1989;Bishop 1991;Rabbitts 1994;Weinberg 1994). In fact, many of the genes that are mutated or lost in cancer cells, including both the oncogenes and tumor suppressers, encode proteins that are crucial regulators for both intra-and intercellular signal transduction (Croce 1987;Alitalo et al. 1988;Bos 1989;Bishop 1991;Rabbitts 1994;Weinberg 1994). This conceptual framework has provided a basis for the development of novel anticancer strategies and therapeutic modalities aimed at inhibiting cancer growth either by blocking mitogenic signal transduction or specifically inducing apoptosis of cancer cells. Although the various approaches have not been clinically validated, these strategies are likely to identify compounds with fewer side effects compared to standard chemotherapeutic agents.