title: Targeting the KRAS variant for treatment of non-small cell lung cancer: potential therapeutic applications.
abstract: Lung cancer is the leading cause of cancer deaths worldwide, with non-small cell lung cancer (NSCLC) accounting for 80% of all lung cancers. Kirsten rat sarcoma viral oncogene homolog (KRAS) is one of the deadliest cancer-related proteins and plays a pivotal role in the most aggressive and lethal human cancers, including lung adenocarcinoma where it represents one of the most frequently mutated oncogene. Although therapeutic progresses have made an impact over the last decade, median survival for patients with advanced lung cancer remains disappointing, with a 5-year worldwide survival rate of <15%. For more than 20 years it has been recognized that constitutively active signaling downstream of KRAS is a fundamental driver of lung tumorigenesis. However, years of pursuit have failed to yield a drug that can safely curb KRAS activity; up to now no approved therapies exist for KRAS-mutant NSCLC. The aim of this review is to discuss the current knowledge of KRAS-mutated NSCLC, touching upon KRAS clinical relevance as a prognostic and predictive biomarker, with an emphasis on novel therapeutic approaches for the treatment of KRAS-variant NSCLC.
authors.affiliation: a Medical Oncology , Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia , Perugia , Italy.
authors.forename: Biagio
authors.initials: B
authors.lastname: Ricciuti
authors.affiliation: a Medical Oncology , Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia , Perugia , Italy.
authors.forename: Giulia Costanza
authors.initials: GC
authors.lastname: Leonardi
authors.affiliation: a Medical Oncology , Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia , Perugia , Italy.
authors.forename: Giulio
authors.initials: G
authors.lastname: Metro
authors.affiliation: b Department of Clinical and Experimental Medicine, Division of Pathology , University of Perugia , Perugia , Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Grignani
authors.affiliation: a Medical Oncology , Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia , Perugia , Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Paglialunga
authors.affiliation: c Department of Experimental Medicine, Division of Pathology and Histology , University of Perugia , Perugia , Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Bellezza
authors.affiliation: a Medical Oncology , Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia , Perugia , Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Baglivo
authors.affiliation: a Medical Oncology , Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia , Perugia , Italy.
authors.forename: Clelia
authors.initials: C
authors.lastname: Mencaroni
authors.affiliation: a Medical Oncology , Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia , Perugia , Italy.
authors.forename: Alice
authors.initials: A
authors.lastname: Baldi
authors.affiliation: a Medical Oncology , Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia , Perugia , Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Zicari
authors.affiliation: a Medical Oncology , Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia , Perugia , Italy.
authors.forename: Lucio
authors.initials: L
authors.lastname: Crinò
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics*; D000077192:Adenocarcinoma of Lung; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics*; D058990:Molecular Targeted Therapy / Q000379:methods; D009154:Mutation; D011379:Prognosis; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)
keywords: KRAS; NSCLC; mutant allele-specific imbalance; prediction; prognosis; selumetinib; signal transduction; synthetic lethality; targeted therapy