SUNY Downstate Medical Center, Brooklyn, New York.
Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, New York.
Mol Cancer Ther. 2024 Nov 4;23(11):1544-1554. doi: 10.1158/1535-7163.MCT-23-0725.
Advances in tumor molecular profiling have uncovered shared genomic and proteomic alterations across tumor types that can be exploited therapeutically. A biomarker-driven, disease-agnostic approach to oncology drug development can maximize the reach of novel therapeutics. To date, eight drug-biomarker pairs have been approved for the treatment of patients with advanced solid tumors with specific molecular profiles. Emerging biomarkers with the potential for clinical actionability across tumor types include gene fusions involving NRG1, FGFR1/2/3, BRAF, and ALK and mutations in TP53 Y220C, KRAS G12C, FGFR2/3, and BRAF non-V600 (class II). We explore the growing evidence for clinical actionability of these biomarkers in patients with advanced solid tumors.
肿瘤分子谱分析的进展揭示了 across tumor types 的共享基因组和蛋白质组改变，这些改变可被用于治疗。一种基于 biomarker 的、与疾病无关的肿瘤药物开发方法可以最大限度地扩大 novel therapeutics 的应用范围。迄今为止，已有八种 drug-biomarker 对被批准用于治疗具有特定分子特征的 advanced solid tumors 患者。在 across tumor types 中具有潜在临床可操作性的新兴 biomarker 包括涉及 NRG1、FGFR1/2/3、BRAF 和 ALK 的基因融合以及 TP53 Y220C、KRAS G12C、FGFR2/3 和 BRAF non-V600（II 类）的突变。我们探讨了这些 biomarker 在 advanced solid tumors 患者中具有临床可操作性的证据。
