Blanchet Anais, Bourgmayer Agathe, Kurtz Jean-Emmanuel, Mellitzer Georg, Gaiddon Christian
Laboratory "Streinth" (STress REsponse and INnovative Therapies in Cancer), Inserm UMR_S 1113, IRFAC, ITI InnoVec, Université de Strasbourg, 67200 Strasbourg, France.
ICANS (Institut du Cancer Strasbourg Europe), 67200 Strasbourg, France.
Cancers (Basel). 2021 Feb 22;13(4):916. doi: 10.3390/cancers13040916.
Gastric cancer is one of the most aggressive cancers, with a median survival of 12 months. This illustrates its complexity and the lack of therapeutic options, such as personalized therapy, because predictive markers do not exist. Thus, gastric cancer remains mostly treated with cytotoxic chemotherapies. In addition, less than 20% of patients respond to immunotherapy. mutations are particularly frequent in gastric cancer (±50% and up to 70% in metastatic) and are considered an early event in the tumorigenic process. Alterations in the expression of other members of the p53 family, i.e., p63 and p73, have also been described. In this context, the role of the members of the p53 family and their isoforms have been investigated over the years, resulting in conflicting data. For instance, whether mutations of or the dysregulation of its homologs may represent biomarkers for aggressivity or response to therapy still remains a matter of debate. This uncertainty illustrates the lack of information on the molecular pathways involving the p53 family in gastric cancer. In this review, we summarize and discuss the most relevant molecular and clinical data on the role of the p53 family in gastric cancer and enumerate potential therapeutic innovative strategies.
胃癌是最具侵袭性的癌症之一，中位生存期为12个月。这说明了其复杂性以及缺乏个性化治疗等治疗选择，因为不存在预测性标志物。因此，胃癌主要仍采用细胞毒性化疗进行治疗。此外，不到20%的患者对免疫疗法有反应。在胃癌中，（基因）突变尤为常见（在转移性胃癌中约为50%，高达70%），并且被认为是肿瘤发生过程中的早期事件。p53家族其他成员即p63和p73的表达改变也有相关描述。在此背景下，多年来一直在研究p53家族成员及其异构体的作用，结果产生了相互矛盾的数据。例如，（基因）突变或其同源物的失调是否可能代表侵袭性或治疗反应的生物标志物，仍然存在争议。这种不确定性说明了在胃癌中涉及p53家族的分子途径方面缺乏信息。在本综述中，我们总结并讨论了关于p53家族在胃癌中作用的最相关分子和临床数据，并列举了潜在的治疗创新策略。
