title: Across the universe of K-RAS mutations in non-small-cell-lung cancer.
abstract: RAS family proteins are important signaling molecules that regulate cell growth, survival and differentiation by coupling receptor activation to downstream effector pathways. Three distinct genes encode for the three different proteins H-, K-, and N- RAS. These proteins share high sequence homology, particularly at the N-Terminal domain. Among them, K-RAS is one of the most frequently mutated in human cancer. The majority of the mutations present in K-RAS are at codon 12 (from 80 to 100%) followed by codon 13 and 61. In all cases, aminoacid change leads to a constitutively activated protein. K-RAS mutations have a role in tumor development as well as in tumor progression and resistance. Despite the various studies which have been published, the prognostic and predictive role of K-RAS mutations is still under debate. Keeping in mind that the glycine present at position 12 can be substituted by valine, aspartic acid or cysteine, it could be well understood that each different substitution plays a different role in K-RAS-dependent processes. The present article focuses on the molecular and biological characteristics of K-RAS protein, its role in NSCLC tumor development and progression. We also present an overview of the preclinical models both in vitro and in vivo available to determine the role of K-RAS in tumor progression and response to treatment and on the recent results obtained in this field. Finally, we have considered the impact of KRAS mutations in clinical practice, analyzing the different recent trials that have taken into consideration K-RAS.
authors.forename: Sheila
authors.initials: S
authors.lastname: Piva
authors.forename: Monica
authors.initials: M
authors.lastname: Ganzinelli
authors.forename: Marina Chiara
authors.initials: MC
authors.lastname: Garassino
authors.forename: Elisa
authors.initials: E
authors.lastname: Caiola
authors.forename: Gabriella
authors.initials: G
authors.lastname: Farina
authors.forename: Massimo
authors.initials: M
authors.lastname: Broggini
authors.affiliation: Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian, 1 20123 Milan, Italy. marina.garassino@istitutotumori.mi.it.
authors.forename: Mirko
authors.initials: M
authors.lastname: Marabese
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D018631:ras Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
chemical_list: D018631:ras Proteins