title: TP53 and MDM2 genetic alterations in non-small cell lung cancer: Evaluating their prognostic and predictive value.
abstract: The p53 pathway has been extensively studied for its role in carcinogenesis. Disruption of the pathway occurs in more than half of all cancers, often leading to a worse prognosis for the patient. In recent years several compounds have been successfully developed to target and restore the p53 pathway, either by blocking the MDM2-p53 interaction, restoring wild type conformation of mutant p53, or exploiting the presence of mutant p53 by blocking DNA damage repair pathways. In this review the known data on the role of p53 on prognosis and response to commonly used chemotherapeutics in non-small cell lung cancer is summarized. The focus is on the presence of genetic alterations in the TP53 or MDM2 gene, p53's main negative regulator. In addition, promising therapeutic options will be discussed in relation to specific alterations in the p53 pathway.
authors.affiliation: Center for Oncological Research (CORE), University of Antwerp, Antwerp, Belgium; Department of Pathology, Antwerp University Hospital, Antwerp, Belgium.
authors.forename: Christophe
authors.initials: C
authors.lastname: Deben
authors.affiliation: Center for Oncological Research (CORE), University of Antwerp, Antwerp, Belgium; Department of Pathology, Antwerp University Hospital, Antwerp, Belgium.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Deschoolmeester
authors.affiliation: Center for Oncological Research (CORE), University of Antwerp, Antwerp, Belgium.
authors.forename: Filip
authors.initials: F
authors.lastname: Lardon
authors.affiliation: Department of Medical Oncology, Antwerp University Hospital, Antwerp, Belgium; Phase-1 Early Clinical Trials Unit, Antwerp University Hospital, Antwerp, Belgium. Electronic address: christian.rolfo@uza.be.
authors.forename: Christian
authors.initials: C
authors.lastname: Rolfo
authors.affiliation: Center for Oncological Research (CORE), University of Antwerp, Antwerp, Belgium; Department of Pathology, Antwerp University Hospital, Antwerp, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: Pauwels
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D009154:Mutation; D011237:Predictive Value of Tests; D011379:Prognosis; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2
keywords: MDM2; NSCLC; P53; Predictive; Prognosis