Inhibition of ras oncogene: A novel approach to antineoplastic therapy

The most frequently detected oncogene alterations, both in animal and human cancers, are the mutations in the ras oncogene family. These oncogenes are mutated or overexpressed in many human tumors, with a high incidence in tu mors of the pancreas, thyroid, colon, lung and certain types of leukemia. R as is a small guanine nucleotide binding protein that transduces biological information from the cell surface to cytoplasmic components within cells. The signal is transduced to the cell nucleus through second messengers, and it ultimately induces cell division. Oncogenic forms of p21(ras) lead to u nregulated, sustained signaling through downstream effecters. The ras famil y of oncogenes is involved in the development of both primary tumors and me tastases making it a good therapeutic target. Several therapeutic approache s to cancer have been developed pointing to reducing the altered gene produ ct or to eliminating its biological function: (1) gene therapy with ribozym es, which are able to break down specific RNA sequences, or with antisense oligonucleotides, (2) immunotherapy through passive or active immunization protocols, and (3) inhibition of p21(ras) farnesylation either by inhibitio n of farnesyl transferase or synthesis inhibition of farnesyl moieties. Cop yright (C) 2000 National Science Council, ROC and S. Karger AG, Basel.