ABSTRACT
The RAS proteins control signalling pathways that are key regulators of several aspects of normal cell growth and malignant transformation. They are aberrant in most human tumours due to activating mutations in the RAS genes themselves or to alterations in upstream or downstream signalling components. Rational therapies that target the RAS pathways might inhibit tumour growth, survival and spread. Several of these new therapeutic agents are showing promise in the clinic and many more are being developed.
Subject(s)
Antineoplastic Agents/pharmacology , GTP Phosphohydrolase Activators/metabolism , Genes, ras , Neoplasms/drug therapy , Signal Transduction/drug effects , ras Proteins/metabolism , Animals , Drug Design , GTP Phosphohydrolase Activators/antagonists & inhibitors , Humans , Neoplasms/metabolism , ras Proteins/geneticsABSTRACT
A dynamic equilibrium or is responsible for the proper function of a living organism. Physiological events regulating proliferation, apoptosis, differentiation, and cell arrest, modulates the correct homeostasis and functionality of all tissues. Cancer is a consequence of a disorder in these sequential events, which results in the alteration of the ratio between cell death, cell differentiation and cell proliferation that ultimately leads to an increase in the number of dysregulated cells. Most of the processes which control the are regulated by signalling pathways, whose components are currently being explored as potential targets for the design of antitumoral drugs. Many in vivo studies have shown that Ras and Rho proteins are key modulators of mitogenic signalling, and are involved in the carcinogenesis of several human tumors. The development of recent drugs that elicit antitumoral activity by blocking some of the Ras and/or Rho effects, is discussed in this review.
