title: Targeting KRAS mutated non-small cell lung cancer: A history of failures and a future of hope for a diverse entity.
abstract: Lung cancer remains the leading cause of cancer-related deaths in both men and women. However, the discovery of several oncogenic driver mutations and the development of immune checkpoint inhibitors resulted in improved clinical outcomes for most patients. Although activating KRAS mutations are the most common recurring molecular events in lung adenocarcinoma, little progress has been made during the past decades with no new agents being approved for this indication. The elucidation of the underlying biology of this diverse patient subgroup offers great potential and renewed hope regarding the rational development, rigorous evaluation and subsequent approval of novel targeted agents and combinations which will effectively suppress compensatory escape routes and the emergence of resistance, issues that have plagued previous attempts. Here, we review in a structured manner all aspects of KRAS positive non-small cell lung cancer, including the molecular biology, clinicopathologic characteristics, the prognostic and predictive value of KRAS mutations, as well as previous and contemporary approaches towards the treatment of this elusive target.
authors.affiliation: Department of Oncology - Pathology, Karolinska Institutet, Sweden; Hellenic Oncology Research Group (HORG), Greece.
authors.forename: Alexios
authors.initials: A
authors.lastname: Matikas
authors.affiliation: University Hospital of Ioannina, Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Mistriotis
authors.affiliation: Laboratory of Translational Oncology, University of Crete, School of Medicine, Greece; Hellenic Oncology Research Group (HORG), Greece.
authors.forename: Vasilios
authors.initials: V
authors.lastname: Georgoulias
authors.affiliation: Department of Medical Oncology, University General Hospital of Heraklion, Greece; Laboratory of Translational Oncology, University of Crete, School of Medicine, Greece; Hellenic Oncology Research Group (HORG), Greece. Electronic address: kotsakis@uoc.gr.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Kotsakis
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics*; D009154:Mutation; D011379:Prognosis; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)
keywords: KRAS; MEK; NSCLC; Predictive; Prognostic; Targeted therapy