title: New druggable targets in the Ras pathway?
abstract: Ras proteins are key elements in the regulation of cellular proliferation, differentiation and survival. Mutational activation of Ras or of components of its effector pathways are detected in one-third of human cancers and are essential for the genesis and maintenance of the tumoral phenotype. Research efforts have been dedicated to the development of therapeutic agents that inhibit aberrant Ras signals and, subsequently, tumor progression. However, many of these initiatives have proven less successful than expected. This review summarizes the current status of developments in Ras research, the challenges that have arisen during preclinical and clinical stages, and how novel approaches to targeting Ras pathways have introduced new strategies toward the development of antitumoral agents that are alternative or complementary to those currently in use. These new approaches would be aimed at disrupting key protein-protein interactions that are essential for the conveyance of Ras aberrant signals or would be directed against new proteins recently demonstrated to be critical participants in Ras-regulated pathways.
authors.affiliation: Universidad de Cantabria, Instituto de Biomedicina y Biotecnología de Cantabria, Consejo Superior de Investigaciones Científicas, IDICAN, Departamento de Biología Molecular, Facultad de Medicina, c/Cardenal Herrera Oria s/n, Santander, 39011 Cantabria, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Matallanas
authors.forename: Piero
authors.initials: P
authors.lastname: Crespo
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D008954:Models, Biological; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D018631:ras Proteins