Ablain Julien, Poirot Brigitte, Esnault Cécile, Lehmann-Che Jacqueline, de Thé Hugues
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.
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.
Cold Spring Harb Perspect Med. 2015 Dec 4;6(1):a026260. doi: 10.1101/cshperspect.a026260.
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.
尽管在特定肿瘤中p53信号通路的完整性被认为是对治疗反应的关键决定因素,但大多数临床研究未能将p53状态与治疗结果联系起来。在此,我们呈现两种相反的情况:一种是p53是靶向白血病治疗治愈的关键效应因子,另一种是在晚期乳腺癌中,p53失活是剂量密集化疗临床疗效所必需的。如果p53促进或阻断治疗反应,那么治疗必须根据个体肿瘤中的p53状态进行调整。