p53 as an Effector or Inhibitor of Therapy Response

Julien Ablain; Brigitte Poirot; Cécile Esnault; Jacqueline Lehmann-Che; Hugues de Thé

doi:10.1101/cshperspect.a026260

p53 as an Effector or Inhibitor of Therapy Response

Cold Spring Harb Perspect Med. 2015 Dec 4;6(1):a026260. doi: 10.1101/cshperspect.a026260.

Authors

Julien Ablain¹, Brigitte Poirot², Cécile Esnault¹, Jacqueline Lehmann-Che², Hugues de Thé³

Affiliations

¹ Université Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Hôpital St. Louis, 75475 Paris, France INSERM UMR 944, Equipe Labellisée par la Ligue Nationale contre le Cancer, Hôpital St. Louis, 75475 Paris, France CNRS UMR 7212, Hôpital St. Louis, 75475 Paris, France.
² Université Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Hôpital St. Louis, 75475 Paris, France INSERM UMR 944, Equipe Labellisée par la Ligue Nationale contre le Cancer, Hôpital St. Louis, 75475 Paris, France CNRS UMR 7212, Hôpital St. Louis, 75475 Paris, France Assistance Publique des Hôpitaux de Paris, Oncologie Moléculaire, Hôpital St. Louis, 75475 Paris, France.
³ Université Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Hôpital St. Louis, 75475 Paris, France INSERM UMR 944, Equipe Labellisée par la Ligue Nationale contre le Cancer, Hôpital St. Louis, 75475 Paris, France CNRS UMR 7212, Hôpital St. Louis, 75475 Paris, France Assistance Publique des Hôpitaux de Paris, Oncologie Moléculaire, Hôpital St. Louis, 75475 Paris, France Collège de France, 75005 Paris, France.

Abstract

Although integrity of the p53 signaling pathway in a given tumor was expected to be a critical determinant of response to therapies, most clinical studies failed to link p53 status and treatment outcome. Here, we present two opposite situations: one in which p53 is an essential effector of cure by targeted leukemia therapies and another one in advanced breast cancers in which p53 inactivation is required for the clinical efficacy of dose-dense chemotherapy. If p53 promotes or blocks therapy response, therapies must be tailored on its status in individual tumors.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Antineoplastic Combined Chemotherapy Protocols / therapeutic use
Arsenic Trioxide
Arsenicals / administration & dosage
Breast Neoplasms / drug therapy
Breast Neoplasms / metabolism*
Female
Humans
Leukemia, Promyelocytic, Acute / drug therapy
Leukemia, Promyelocytic, Acute / genetics*
Leukemia, Promyelocytic, Acute / metabolism
Molecular Targeted Therapy
Oncogene Proteins, Fusion / genetics*
Oxides / administration & dosage
Treatment Outcome
Tretinoin / administration & dosage
Tumor Suppressor Protein p53 / metabolism*

Substances

Arsenicals
Oncogene Proteins, Fusion
Oxides
TP53 protein, human
Tumor Suppressor Protein p53
promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein
Tretinoin
Arsenic Trioxide