Evidence that p53-mediated cell-cycle-arrest inhibits chemotherapeutic treatment of ovarian carcinomas.
PLoS One, 2007/5/16;2(5):e441.
Moreno CS[1], Matyunina L, Dickerson EB, Schubert N, Bowen NJ, Logani S, Benigno BB, McDonald JF
Affiliations
PMID: 17505532
Impact factor: 3.752
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-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.
MeSH terms
Antineoplastic Agents; Cell Cycle; Female; Genes, p53; Humans; Loss of Heterozygosity; Models, Theoretical; Ovarian Neoplasms; Reverse Transcriptase Polymerase Chain Reaction
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