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[分子标志物对结直肠癌肿瘤外科手术的影响]

[Influence of molecular markers on oncological surgery of colorectal cancer].

作者信息

Nöpel-Dünnebacke Stefanie, Conradi Lena-Christin, Reinacher-Schick Anke, Ghadimi Michael

机构信息

Medizinische Klinik V Hämatologie, Onkologie und Palliativmedizin, St. Josef-Hospital, Klinikum der Ruhr-Universität Bochum, Gudrunstraße 56, 44791, Bochum, Deutschland.

Klinik für Allgemein‑, Viszeral- und Kinderchirurgie, Universitätsmedizin Göttingen, Göttingen, Deutschland.

出版信息

Chirurg. 2021 Nov;92(11):986-995. doi: 10.1007/s00104-021-01486-7. Epub 2021 Aug 27.

Abstract

Colorectal cancer (CRC) is still a very common disease and one of the best characterized malignancies on a molecular level. Interdisciplinary and multimodal treatment strategies should be preferred. In addition to surgical resection in localized stages as well as metastasectomy for oligometastatic advanced stages, neoadjuvant chemoradiotherapy for localized rectal cancer and cytostatic treatment, targeted treatment approaches should also be considered. This overview presents established and novel prognostic and predictive molecular markers of (metastasized) CRC and describes these as targeted therapy options. The determination of high microsatellite instability (MSI-H) has a therapeutic influence when planning adjuvant therapy and also now in the treatment of metastatic CRC. Furthermore, circulating tumor DNA represents a promising marker with respect to a recurrence in early as well as in advanced stages of disease. In addition to the RAS and BRAF mutation status and the localization of the primary tumor, an MSI‑H is also important with respect to the treatment strategy and should be determined before initiation of first-line treatment in metastasized CRC. New pharmaceutical approaches enable targeted interventions at the immunological or molecular level. The understanding of CRC as a heterogeneous disease has been increased using recently established analyses at the molecular level; however, it also generated many hypotheses that require further evaluation with respect to their clinical importance. Special attention is paid to patients affected by hereditary syndromes because of the early onset of disease and the considerable consequences individually and for the patient's family.

摘要

结直肠癌(CRC)仍然是一种非常常见的疾病,并且是分子水平上特征最明确的恶性肿瘤之一。应优先采用多学科和多模式治疗策略。除了局部阶段的手术切除以及寡转移晚期阶段的转移灶切除术、局部直肠癌的新辅助放化疗和细胞抑制治疗外,还应考虑靶向治疗方法。本综述介绍了已确立的和新的(转移)结直肠癌预后和预测分子标志物,并将其描述为靶向治疗选择。确定高微卫星不稳定性(MSI-H)在规划辅助治疗时以及目前在转移性结直肠癌的治疗中都具有治疗意义。此外,循环肿瘤DNA对于疾病早期和晚期的复发都是一个有前景的标志物。除了RAS和BRAF突变状态以及原发肿瘤的定位外,MSI-H对于治疗策略也很重要,并且应在转移性结直肠癌一线治疗开始前确定。新的药物治疗方法能够在免疫或分子水平上进行靶向干预。通过最近在分子水平上建立的分析,对结直肠癌作为一种异质性疾病的理解有所增加;然而,这也产生了许多假设,需要就其临床重要性进行进一步评估。由于疾病发病早以及对患者个人和家庭造成的重大影响,患有遗传性综合征的患者受到特别关注。

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