title: Oncogenes in non-small-cell lung cancer: emerging connections and novel therapeutic dynamics.
abstract: Non-small-cell lung cancer is a heterogeneous disease that is difficult to treat. Through efforts to define the molecular mechanisms involved in lung oncogenesis, molecularly targeted approaches for patients with lung cancer have now reached the clinical arena. Despite elucidation of some molecular mechanisms of lung carcinogenesis, prognosis for patients remains poor. This Review aims to highlight the functional associations between key oncogenes that drive lung tumorigenesis and are distinct targetable molecules. Oncogenes are defined by acquisition of mutations, which results in a dominant gain-of-function of the targeted protein. In this situation, a single mutated allele is sufficient to induce malignant transformation. Importantly, tumours become addicted to particular genetic alterations that cause oncogene activation and the continued expression of the signalling. An increasing amount of evidence sustains the rationale for targeting of oncogenic pathways rather than a single oncogene. A clear priority for both researchers and clinicians is to better understand the complexity of biological networks underlying lung cancer pathogenesis. This paradigmatic shift in tailoring therapies should effectively improve outcomes for patients.
authors.affiliation: Department of Molecular Medicine, Division of Pneumology, Laboratory of Biochemistry and Genetics, University and Fondazione IRCCS Policlinico, San Matteo, Pavia, Italy; Institute for Cancer Research at Candiolo, Candiolo, Italy. Electronic address: g.stella@smatteo.pv.it.
authors.forename: Giulia M
authors.initials: GM
authors.lastname: Stella
authors.affiliation: Department of Molecular Medicine, Division of Pneumology, Laboratory of Biochemistry and Genetics, University and Fondazione IRCCS Policlinico, San Matteo, Pavia, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Luisetti
authors.affiliation: University of Pavia, Policlinico di Monza, Monza, Italy.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Pozzi
authors.affiliation: Institute for Cancer Research at Candiolo, Candiolo, Italy.
authors.forename: Paolo M
authors.initials: PM
authors.lastname: Comoglio
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology / Q000628:therapy; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000235:genetics; D015507:Drugs, Investigational / Q000494:pharmacology; D056726:Genetic Association Studies; D018740:Genetic Heterogeneity; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy; D058990:Molecular Targeted Therapy / Q000379:methods / Q000639:trends; D009154:Mutation; D009857:Oncogenes; D011379:Prognosis; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects; D014178:Translocation, Genetic / Q000187:drug effects
chemical_list: D015507:Drugs, Investigational