精准医学已经彻底改变了癌症治疗的方式；然而，可行的生物标志物仍然稀缺。为了解决这个问题，我们开发了肿瘤学生物标志物发现（OncoBird）框架，用于分析随机对照临床试验中的分子和生物标志物景观。OncoBird基于单基因或相互排斥的基因突变来鉴定生物标志物，可以独立使用或者结合肿瘤亚型进行分析，并通过治疗相互作用来评估预测性组分。在这里，我们利用开放标签、随机第三期试验（FIRE-3, AIO KRK-0306），对转移性结直肠癌患者进行了研究，患者分别接受赛曲单抗或贝伐单抗与5-氟尿嘧啶、叶酸和铱替考汀（FOLFIRI）的联合治疗。我们系统地鉴定出了五个具有预测性组分的生物标志物，例如，携带chr20q扩增或互斥ERK信号突变的肿瘤患者与接受贝伐单抗相比可以从赛曲单抗获益。总之，OncoBird能够表征分子景观并概述可行的生物标志物，这适用于任何分子特征化的随机对照试验。© 2023. Springer Nature Limited.

Precision medicine has revolutionised cancer treatments; however, actionable biomarkers remain scarce. To address this, we develop the Oncology Biomarker Discovery (OncoBird) framework for analysing the molecular and biomarker landscape of randomised controlled clinical trials. OncoBird identifies biomarkers based on single genes or mutually exclusive genetic alterations in isolation or in the context of tumour subtypes, and finally, assesses predictive components by their treatment interactions. Here, we utilise the open-label, randomised phase III trial (FIRE-3, AIO KRK-0306) in metastatic colorectal carcinoma patients, who received either cetuximab or bevacizumab in combination with 5-fluorouracil, folinic acid and irinotecan (FOLFIRI). We systematically identify five biomarkers with predictive components, e.g., patients with tumours that carry chr20q amplifications or lack mutually exclusive ERK signalling mutations benefited from cetuximab compared to bevacizumab. In summary, OncoBird characterises the molecular landscape and outlines actionable biomarkers, which generalises to any molecularly characterised randomised controlled trial.© 2023. Springer Nature Limited.