Oncogenes

Abstract

Overview The initiation and progression of human neoplastic diseases is a multistep process involving the accumulation of genetic changes in somatic cells. These genetic changes typically consist of the activation of cooperating oncogenes and the inactivation of tumor suppressor genes, which both appear necessary for a complete neoplastic phenotype. Oncogenes are altered versions of normal cellular genes called proto‐oncogenes, usually involved in the regulation of cell growth and activated by mutation, chromosomal rearrangement, or gene amplification. In this chapter, at first we will describe the methods that have been applied by the researchers for the discovery and the identification of oncogenes. Then we will present the genetic mechanisms of proto‐oncogenes activation (point mutations, gene amplifications, chromosomal rearrangements) with several examples, and we will describe the role played by oncogenes in the initiation and progression of various cancers. The identification of oncogene abnormalities has provided tools for the molecular diagnosis and monitoring of cancer. Most important, oncogenes represent potential targets for new types of cancer therapies, which are continuously discovered and tested in clinical trials. The goal of these new drugs is to kill cancer cells selectively while sparing normal cells. These new therapies display an evident benefit for the treatment of several neoplastic diseases that were, before targeted therapies development, very hard to be treated and cured. However, they are not able to kill 100% of neoplastic cells, essentially due to the occurrence of mechanisms of secondary resistance. In the last part of the chapter, we will review all the genes for which a targeted therapy has been developed.