Wt P53 Impairs Response to Chemotherapy: Make Lemonade to Spare Normal Cells

Overview

Journal Oncotarget

Specialty Oncology

Date 2012 Jul 18

PMID 22802145

Citations 13

Authors

Mikhail V Blagosklonny

Affiliations

Soon will be listed here.

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.

Citing Articles

The imidazoacridinone C-1311 induces p53-dependent senescence or p53-independent apoptosis and sensitizes cancer cells to radiation.

Skwarska A, Ramachandran S, Dobrynin G, Leszczynska K, Hammond E Oncotarget. 2017; 8(19):31187-31198.

PMID: 28415717 PMC: 5458200. DOI: 10.18632/oncotarget.16102.

Silencing of CDK2, but not CDK1, separates mitogenic from anti-apoptotic signaling, sensitizing p53 defective cells for synthetic lethality.

Nekova T, Kneitz S, Einsele H, Bargou R, Stuhler G Cell Cycle. 2016; 15(23):3203-3209.

PMID: 27831832 PMC: 5176141. DOI: 10.1080/15384101.2016.1241915.

Cooperation of Nutlin-3a and a Wip1 inhibitor to induce p53 activity.

Sriraman A, Radovanovic M, Wienken M, Najafova Z, Li Y, Dobbelstein M Oncotarget. 2016; 7(22):31623-38.

PMID: 27183917 PMC: 5077964. DOI: 10.18632/oncotarget.9302.

Mdm2 inhibition confers protection of p53-proficient cells from the cytotoxic effects of Wee1 inhibitors.

Li Y, Saini P, Sriraman A, Dobbelstein M Oncotarget. 2015; 6(32):32339-52.

PMID: 26431163 PMC: 4741697. DOI: 10.18632/oncotarget.5891.

Exploiting replicative stress to treat cancer.

Dobbelstein M, Sorensen C Nat Rev Drug Discov. 2015; 14(6):405-23.

PMID: 25953507 DOI: 10.1038/nrd4553.

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