Introduction

Molecular profiling has led to significantly longer survival in metastatic colorectal cancer (mCRC) patients. Clinical guidelines recommend testing for KRAS/NRAS, BRAF and MSI status, and new biomarkers such as HER2 amplification and NTRK fusions have emerged more recently in refractory CRC, supported by overwhelming clinical relevance. These biomarkers can guide treatment management to improve clinical outcomes in these patients.

Areas covered

Preclinical and clinical data over the last decade were reviewed for known and novel biomarkers with clinical implications in refractory CRC. Molecular alterations are described for classic and novel biomarkers, and data for completed and ongoing studies with targeted and immunotherapies are presented.

Expert opinion

Use of targeted therapies based on biomarker testing in CRC has enabled impressive improvements in clinical outcomes in refractory patients. BRAF, MSI, NRAS and KRAS should be tested upfront in all patients given their indisputable therapeutic implications. Other molecular alterations such as HER2 and NTRK are emerging. Testing for these alterations may further improve outcomes for refractory CRC patients. Nonetheless, many key aspects remain to be defined including the optimal timing and technique for testing, the most adequate panel, and whether all patients should be tested for all alterations.

中文翻译：

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将传统和新兴生物标志物纳入转移性结直肠癌的临床管理：更新。

介绍

分子谱分析显着延长了转移性结直肠癌 (mCRC) 患者的生存期。临床指南建议检测 KRAS/NRAS、BRAF 和 MSI 状态，并且最近在难治性 CRC 中出现了新的生物标志物，例如 HER2 扩增和 NTRK 融合，这得到了压倒性的临床相关性的支持。这些生物标志物可以指导治疗管理，以改善这些患者的临床结果。

覆盖区域

回顾了过去十年的临床前和临床数据，寻找对难治性 CRC 具有临床意义的已知和新型生物标志物。描述了经典和新型生物标志物的分子改变，并提供了已完成和正在进行的靶向和免疫疗法研究的数据。

专家意见

在 CRC 中使用基于生物标志物检测的靶向治疗已经能够显着改善难治性患者的临床结果。鉴于 BRAF、MSI、NRAS 和 KRAS 具有无可争辩的治疗意义，应在所有患者中预先进行测试。其他分子改变如 HER2 和 NTRK 正在出现。检测这些改变可能会进一步改善难治性 CRC 患者的预后。尽管如此，许多关键方面仍有待确定，包括检测的最佳时机和技术、最合适的面板以及是否应检测所有患者的所有改变。