The Role of p53 Dysfunction in Colorectal Cancer and Its Implication for Therapy.
The Role of p53 Dysfunction in Colorectal Cancer and Its Implication for Therapy.
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p53功能障碍在结直肠癌中的作用及其对治疗的影响。
DOI：
10.3390/cancers13102296
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发表时间：
2021-05-11
期刊：
影响因子：
5.2
通讯作者：
Moehler M
中科院分区：
文献类型：
--
作者：
Michel M;Kaps L;Maderer A;Galle PR;Moehler M
尽管在过去的几十年里，预防性医学检查取得了显着进展，但结直肠癌（CRC）仍然是全球最常见和最致命的癌症之一。需要了解CRC中的突变景观，以开发新的突变组导向疗法，其疗效比目前的治疗标准方案更强，副作用更少。CRC的致癌作用是一个多基因驱动的过程，其中癌前细胞连续积累关键的肿瘤发生相关突变。在这里，肿瘤抑制基因p53的失活是肿瘤发生过程中的标志性事件。p53的突变影响患者的预后，使靶向治疗如免疫治疗的使用成为可能。p53的改变不仅影响癌细胞的肿瘤生物学，而且影响周围的肿瘤微环境（TME）。结直肠癌（CRC）是世界范围内最常见和最致命的癌症之一。CRC的致癌作用是基于突变的逐步积累，导致癌基因的激活或抑制基因的失活。遗传稳定性的丧失触发原癌基因的激活（例如，KRAS）和肿瘤抑制基因（即TP53和APC）的失活，它们共同驱动腺瘤向腺癌的转变。一方面，p53突变赋予对经典化疗的抗性，但另一方面，它们为免疫治疗打开了大门，因为p53突变的肿瘤富含新抗原。TP53基因产物p53的异常功能也影响肿瘤微环境中的基质和非基质细胞。癌症相关的成纤维细胞与其他免疫抑制细胞一起通过p53介导的肿瘤信号传导成为肿瘤的宝贵资产。在这篇综述中，我们讨论了p53突变在CRC治疗，治疗反应和个性化医疗方面的多方面影响。
Despite remarkable progress being made by preventive medical check-ups in the last decades, colorectal cancer (CRC) remains one of the most frequent and deadliest cancers worldwide. An understanding of the mutational landscape in CRC is needed to develop new mutanome-directed therapies with stronger efficacy and less side-effects than current therapeutic standard regimes. Carcinogenesis in CRC is a multi-gene driven process, where premalignant cells accumulate successively key tumorigenesis-related mutations. Here, inactivation of the tumor suppressor gene p53 is a hallmark event during tumorigenesis. Mutations of p53 impact the prognosis of patients, enabling the use of targeted therapies such as immune therapy. Alterations of p53 affect not only the tumor biology of cancer cells but also the surrounding tumor microenvironment (TME). Colorectal cancer (CRC) is one of the most common and fatal cancers worldwide. The carcinogenesis of CRC is based on a stepwise accumulation of mutations, leading either to an activation of oncogenes or a deactivation of suppressor genes. The loss of genetic stability triggers activation of proto-oncogenes (e.g., KRAS) and inactivation of tumor suppression genes, namely TP53 and APC, which together drive the transition from adenoma to adenocarcinoma. On the one hand, p53 mutations confer resistance to classical chemotherapy but, on the other hand, they open the door for immunotherapy, as p53-mutated tumors are rich in neoantigens. Aberrant function of the TP53 gene product, p53, also affects stromal and non-stromal cells in the tumor microenvironment. Cancer-associated fibroblasts together with other immunosuppressive cells become valuable assets for the tumor by p53-mediated tumor signaling. In this review, we address the manifold implications of p53 mutations in CRC regarding therapy, treatment response and personalized medicine.
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影响因子：
6
作者：
Bockamp E;Rosigkeit S;Siegl D;Schuppan D
通讯作者：
Schuppan D
DOI：
10.1136/bmj.d6617
发表时间：
2011-11-10
期刊：
BMJ (Clinical research ed.)
影响因子：
--
作者：
Aune D;Chan DS;Lau R;Vieira R;Greenwood DC;Kampman E;Norat T
通讯作者：
Norat T
DOI：
10.1016/j.bbalip.2018.07.011
发表时间：
2018-10-01
影响因子：
4.8
作者：
Brachtendorf, Sebastian;Wanger, Ruth Anna;Groesch, Sabine
通讯作者：
Groesch, Sabine
影响因子：
6.4
作者：
Atencio, IA;Grace, M;Warren, R
通讯作者：
Warren, R
影响因子：
11.5
作者：
Boyer, J;McLean, EG;Johnston, PG
通讯作者：
Johnston, PG