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Comment
. 2012 Jun;3(6):601-7.
doi: 10.18632/oncotarget.548.

Wt p53 impairs response to chemotherapy: make lemonade to spare normal cells

Mikhail V Blagosklonny  1
Affiliations
Comment

Wt p53 impairs response to chemotherapy: make lemonade to spare normal cells

Mikhail V Blagosklonny. Oncotarget. 2012 Jun.

Abstract

As published recently in Cancer Cell, p53 impairs the apoptotic response to chemotherapy and clinical outcome in breast cancer. I discuss that, while treating tumors lacking wt p53, this phenomenon can be exploited to protect normal cells from chemotherapy because all normal cells have wt p53. Also, several therapeutic paradigms can be reassessed, including the role of cellular senescence in cancer therapy.

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Figures

Figure 1
Figure 1. Protection of normal cells: From a single drug to ordered combinations
(A) Doxorubicin (Dox) causes G1/G2 arrest (red) in wt p53 cells, whereas cancer cells with mutant p53 enter mitosis (M) and undergo mitotic catastrophe. (B) Low doses of doxorubicin (low DOX) cause a more gentle G1/G2 arrest (orange) in normal cells, whereas cancer cells with mutant p53 enter mitosis (M) and are killed by MI (mitotic inhibitor such as Taxol). (C) Nutlin-3a plus rapamycin cause the gentlest G1/G2 arrest (yellow) in normal cells, whereas cancer cells with mutant p53 enter mitosis (M) and are killed by a highly apoptotic combination of MI plus TRAIL or TNF.
See this image and copyright information in PMC

Comment on

References

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