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转移性结直肠癌患者临床管理中的结直肠癌基因组生物标志物

Colorectal cancer genomic biomarkers in the clinical management of patients with metastatic colorectal carcinoma.

作者信息

Rachiglio Anna Maria, Sacco Alessandra, Forgione Laura, Esposito Claudia, Chicchinelli Nicoletta, Normanno Nicola

机构信息

Cell Biology and Biotherapy Unit, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Naples, Italy.

出版信息

Explor Target Antitumor Ther. 2020;1(1):53-70. doi: 10.37349/etat.2020.00004. Epub 2020 Feb 29.

Abstract

Colorectal carcinoma (CRC) is an heterogeneous disease in which different genetic alterations play a role in its pathogenesis and progression and offer potential for therapeutic intervention. The research on predictive biomarkers in metastatic CRC (mCRC) mainly focused on the identification of biomarkers of response or resistance to anti-epidermal growth factor receptor monoclonal antibodies. In this respect, international guidelines suggest testing mCRC patients only for , and mutations and for microsatellite instability. However, the use of novel testing methods is raising relevant issue related to these biomarkers, such as the presence of sub-clonal mutations or the clinical interpretation of rare no-V600 variants. In addition, a number of novel biomarkers is emerging from recent studies including amplification of , mutations in , and and rearrangements of , , and . Mutations in and the levels of tumor mutation burden also appear as possible biomarkers of response to immunotherapy in CRC. Finally, the consensus molecular subtypes classification of CRC based on gene expression profiling has prognostic and predictive implications. Integration of all these information will be likely necessary in the next future in order to improve precision/personalized medicine in mCRC patients.

摘要

结直肠癌(CRC)是一种异质性疾病,不同的基因改变在其发病机制和进展中发挥作用,并为治疗干预提供了潜力。转移性结直肠癌(mCRC)中预测生物标志物的研究主要集中在鉴定对抗表皮生长因子受体单克隆抗体的反应或耐药生物标志物。在这方面,国际指南建议仅对mCRC患者进行 、 和 突变检测以及微卫星不稳定性检测。然而,新型检测方法的使用引发了与这些生物标志物相关的相关问题,例如亚克隆 突变的存在或罕见的非V600 变体的临床解释。此外,最近的研究还出现了一些新型生物标志物,包括 的扩增、 、 和 中的突变以及 、 、 和 的重排。 和肿瘤突变负担水平的突变也似乎是CRC中免疫治疗反应的可能生物标志物。最后,基于基因表达谱的CRC共识分子亚型分类具有预后和预测意义。为了改善mCRC患者的精准/个性化医疗,未来可能有必要整合所有这些信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10cd/9400741/562e9e17c41b/etat-01-10024-g001.jpg

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