title: VEGF-A Expression Correlates with TP53 Mutations in Non-Small Cell Lung Cancer: Implications for Antiangiogenesis Therapy.
abstract: Bevacizumab is one of the most widely used antiangiogenic drugs in oncology, but the overall beneficial effects of this VEGF-A targeting agent are relatively modest, in part due to the lack of a biomarker to select patients most likely to respond favorably. Several molecular aberrations in cancer influence angiogenesis, including mutations in the tumor suppressor gene TP53, which occur frequently in many human malignancies. In this study, we present a multiple regression analysis of transcriptomic data in 123 patients with non-small cell lung cancer (NSCLC) showing that TP53 mutations are associated with higher VEGF-A expression (P = 0.006). This association was interesting given a recent retrospective study showing longer progression-free survival in patients with diverse tumors who receive bevacizumab, if tumors harbor mutant TP53 instead of wild-type TP53. Thus, our current findings linking TP53 mutation with VEGF-A upregulation offered a mechanistic explanation for why patients exhibit improved outcomes after bevacizumab treatment when their tumors harbor mutant TP53 versus wild-type TP53. Overall, this work warrants further evaluation of TP53 as a ready biomarker to predict bevacizumab response in NSCLC and possibly other tumor types.
authors: Center for Personalized Cancer Therapy, UCSD Moores Cancer Center, La Jolla, California. mschwaederle@ucsd.edu rkurzrock@ucsd.edu Vladimir.LAZAR@gustaveroussy.fr.
authors: Maria
authors: M
authors: Schwaederlé
authors: Gustave Roussy Institute, Villejuif, France. mschwaederle@ucsd.edu rkurzrock@ucsd.edu Vladimir.LAZAR@gustaveroussy.fr.
authors: Vladimir
authors: V
authors: Lazar
authors: Institut Clinique Montsouris, Paris, France.
authors: Pierre
authors: P
authors: Validire
authors: Karolinska Institutet, Stockholm, Sweden.
authors: Johan
authors: J
authors: Hansson
authors: Gustave Roussy Institute, Villejuif, France.
authors: Ludovic
authors: L
authors: Lacroix
authors: Gustave Roussy Institute, Villejuif, France.
authors: Jean-Charles
authors: JC
authors: Soria
authors: Karolinska Institutet, Stockholm, Sweden.
authors: Yudi
authors: Y
authors: Pawitan
authors: Center for Personalized Cancer Therapy, UCSD Moores Cancer Center, La Jolla, California.
authors: Razelle
authors: R
authors: Kurzrock
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism*; D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000068258:Bevacizumab / Q000494:pharmacology / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D009154:Mutation; D059467:Transcriptome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: D020533:Angiogenesis Inhibitors; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab