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- W1964781873 abstract "Studies on the role of TP53 mutation in breast cancer response to chemotherapy are conflicting. Here, we show that, contrary to dogma, MMTV-Wnt1 mammary tumors with mutant p53 exhibited a superior clinical response compared to tumors with wild-type p53. Doxorubicin-treated p53 mutant tumors failed to arrest proliferation, leading to abnormal mitoses and cell death, whereas p53 wild-type tumors arrested, avoiding mitotic catastrophe. Senescent tumor cells persisted, secreting senescence-associated cytokines exhibiting autocrine/paracrine activity and mitogenic potential. Wild-type p53 still mediated arrest and inhibited drug response even in the context of heterozygous p53 point mutations or absence of p21. Thus, we show that wild-type p53 activity hinders chemotherapy response and demonstrate the need to reassess the paradigm for p53 in cancer therapy." @default.
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- W1964781873 date "2012-06-01" @default.
- W1964781873 modified "2023-10-16" @default.
- W1964781873 title "p53-Mediated Senescence Impairs the Apoptotic Response to Chemotherapy and Clinical Outcome in Breast Cancer" @default.
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- W1964781873 doi "https://doi.org/10.1016/j.ccr.2012.04.027" @default.
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