Evidence that p53-Mediated Cell-Cycle-Arrest Inhibits Chemotherapeutic Treatment of Ovarian Carcinomas

• Type of Material: Article
• Authors: Carlos Moreno, Emory University; Lilya Matyunina, Georgia Institute of Technology; Erin B. Dickerson, Georgia Institute of Technology; Nina Schubert, Georgia Institute of Technology; Nathan J. Bowen, Georgia Institute of Technology; Sanjay Logani, Emory University; Benedict B. Benigno, Ovarian Cancer Institute; John F. McDonald, Georgia Institute of Technology
• Language: English
• Date: 2007-05-16
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2007 Moreno et al.
• License: Creative Commons Attribution 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pone.0000441
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 2
• Issue: 5
• Start Page: e441
• End Page: e441
• Grant/Funding Information: This research was supported by grants to JM from the Georgia Cancer Coalition, the Georgia Tech Research Foundation, the Robinson Family Foundation and the Larry and Beth Lawrence Foundation.; CSM received support from R01 CA106826 and the Department of Pathology and Laboratory Medicine, Emory University.
• Keywords: Ovarian cancer; Cancer treatment; Gene expression; Chemotherapy; DNA damage; Surgical oncology; Carcinomas; Surgical and invasive medical procedures; Multidisciplinary Sciences
• Research Categories: Health Sciences, Oncology; Health Sciences, Pathology; Health Sciences, Medicine and Surgery

Abstract

Gene expression profiles of malignant tumors surgically removed from ovarian cancer patients pre-treated with chemotherapy (neo-adjuvant) prior to surgery group into two distinct clusters. One group clusters with carcinomas from patients not pre-treated with chemotherapy prior to surgery (C-L), while the other clusters with non-malignant adenomas (A-QL). We show here that although the C-L cluster is preferentially associated with p53 loss-of-function (LOF) mutations, the C-L cluster cancer patients display a more favorable clinical response to chemotherapy as evidenced by enhanced long-term survivorships. Our results support a model whereby p53 mediated cell-cycle-arrest/DNA repair serves as a barrier to optimal chemotherapeutic treatment of ovarian and perhaps other carcinomas and suggest that inhibition of p53 during chemotherapy may enhance clinical outcome.