Title:
Evidence that p53-mediated cell-cycle-arrest inhibits chemotherapeutic treatment of ovarian carcinomas
Evidence that p53-mediated cell-cycle-arrest inhibits chemotherapeutic treatment of ovarian carcinomas
Author(s)
Moreno, Carlos S.
Matyunina, Lilya V.
Dickerson, Erin B.
Schubert, Nina
Bowen, Nathan J.
Logani, Sanjay
Benigno, Benedict B.
McDonald, John F.
Matyunina, Lilya V.
Dickerson, Erin B.
Schubert, Nina
Bowen, Nathan J.
Logani, Sanjay
Benigno, Benedict B.
McDonald, John F.
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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 pretreated
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.
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Date Issued
2007-05-17
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Article