PLoS ONE (May 2007)

Evidence that p53-mediated cell-cycle-arrest inhibits chemotherapeutic treatment of ovarian carcinomas.

  • Carlos S Moreno,
  • Lilya Matyunina,
  • Erin B Dickerson,
  • Nina Schubert,
  • Nathan J Bowen,
  • Sanjay Logani,
  • Benedict B Benigno,
  • John F McDonald

DOI
https://doi.org/10.1371/journal.pone.0000441
Journal volume & issue
Vol. 2, no. 5
p. e441

Abstract

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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-L). 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.