Inhibition of Cell Growth by Antisense Oligonucleotides Targeting the Growth-Related Protein Kinase c-raf

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. Today it is well recognized that many products of “cancer genes” encode for proteins that regulate normal mitogenesis and apoptosis. Taken together, this indicates that the carcinogenic process may be viewed as a progressive disorder of signal transduction (1 -6 ). In fact, many of the genes that are mutated or lost in cancer cells, including both the oncogenes and tumor suppressors, encode proteins that are crucial regulators for intra- as well as intercellular signal transduction (1 -6 ). This conceptual framework has provided a basis for the development of novel anticancer strategies and therapeutic modalities with the aim to inhibit cancer growth either by blocking mitogenic signal transduction or to specifically induce apoptosis of cancer cells. Although these various approaches have not been validated clinically, these strategies are likely to identify compounds with less side effects compared to standard chemotherapeutic agents.