Inhibitors of the ras oncogene as therapeutic targets

Tumorigenesis is thought to be a result of mutations in multiple genes that control normal cell proliferation, differentiation, and apoptosis. Understanding the processes that govern the signaling pathways of proliferation and the mechanisms by which mutated genes stimulate the expression of the neoplastic phenotype can result in novel, specific therapeutic targets. The improved understanding of the molecular mechanisms of Ras anchorage, post-translational modification, and downstream effector signaling has provided an important background for the development of Ras-targeted anticancer therapy. These therapeutic agents include inhibitors of Ras protein expression, such as antisense oligonucleotides and intracellular antibodies, inhibitors of Ras processing, such as farnesyl transferase inhibitors and geranylgeranylase inhibitors, inhibitors of Ras trafficking, such as heat-shock protein inhibitors, and inhibitors of Ras effector proteins, such as Raf kinase, MEK, and PI3K/Akt kinase inhibitors.