Treatment of BRAF-V600E mutant metastatic colorectal cancer: new insights and biomarkers.

IF 2.9 3区医学 Q2 ONCOLOGY

Expert Review of Anticancer Therapy Pub Date : 2023-07-01 Epub Date: 2023-07-23 DOI:10.1080/14737140.2023.2236794

Javier Ros, Marta Rodríguez-Castells, Nadia Saoudi, Iosune Baraibar, Francesc Salva, Josep Tabernero, Elena Élez

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引用次数: 2

Abstract

Introduction: The presence of a BRAF-V600E mutation in metastatic colorectal cancer (mCRC) is observed in approximately 12% of cases and is associated with poor prognosis and aggressive disease. Unlike melanoma, the development of successful BRAF blockade in colorectal cancer has been complex. The phase III BEACON trial made significant progress in the development of BRAF inhibitors by establishing encorafenib-cetuximab as the new standard of care for patients with mCRC who have progressed to one or two previous lines of treatment. Nonetheless, not all patients respond to encorafenib-based combinations, and some responses are short-lived. Identifying new strategies to boost antitumor activity and improve survival is paramount.

Areas covered: The development of targeted therapy for BRAF-V600E mCRC starting with BRAF inhibitors as monotherapy through novel combinations with anti-VEGF or anti-PD1 agents to enhance antitumor activity is reviewed, with a particular focus on the development of predictive and prognostic biomarkers.

Expert opinion: There is a crucial need to better understand tumor biology and develop accurate and reliable biomarkers to enhance the antitumor activity of encorafenib-based combinations. The RNF43 mutation is an accurate and reliable predictive biomarker of response, and combinations that target crosstalk between the MAPK pathway, the immune system, and WNT pathways seem promising.

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BRAF-V600E突变转移性癌症的治疗：新的见解和生物标志物。

简介：在转移性癌症（mCRC）中，约12%的病例观察到BRAF-V600E突变，并与预后不良和侵袭性疾病有关。与黑色素瘤不同，BRAF阻断在结直肠癌癌症中的成功发展是复杂的。BEACON III期试验在BRAF抑制剂的开发方面取得了重大进展，将安克拉芬尼-西妥昔单抗确立为mCRC患者的新护理标准，这些患者已发展到一种或两种先前的治疗方法。尽管如此，并不是所有的患者都对基于安可非尼的组合有反应，有些反应是短暂的。确定提高抗肿瘤活性和提高生存率的新策略至关重要。涵盖领域：综述了BRAF-V600E mCRC靶向治疗的发展，从BRAF抑制剂作为单一疗法开始，通过与抗VEGF或抗PD1药物的新组合来增强抗肿瘤活性，特别关注预测和预后生物标志物的开发。专家意见：迫切需要更好地了解肿瘤生物学，并开发准确可靠的生物标志物，以增强基于安克拉芬尼的组合的抗肿瘤活性。RNF43突变是一种准确可靠的反应预测生物标志物，针对MAPK途径、免疫系统和WNT途径之间串扰的组合似乎很有前景。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Expert Review of Anticancer Therapy 医学-肿瘤学

CiteScore

5.10

自引率

3.00%

发文量

100

审稿时长

4-8 weeks

期刊介绍： Expert Review of Anticancer Therapy (ISSN 1473-7140) provides expert appraisal and commentary on the major trends in cancer care and highlights the performance of new therapeutic and diagnostic approaches. Coverage includes tumor management, novel medicines, anticancer agents and chemotherapy, biological therapy, cancer vaccines, therapeutic indications, biomarkers and diagnostics, and treatment guidelines. All articles are subject to rigorous peer-review, and the journal makes an essential contribution to decision-making in cancer care. Comprehensive coverage in each review is complemented by the unique Expert Review format and includes the following sections: Expert Opinion - a personal view of the data presented in the article, a discussion on the developments that are likely to be important in the future, and the avenues of research likely to become exciting as further studies yield more detailed results Article Highlights – an executive summary of the author’s most critical points.