Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS, Milan, Italy; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.
Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS, Milan, Italy; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy; Early Drug Development service, Memorial Sloan-Kettering Cancer Center, New York, USA.
Trends Cancer. 2023 Dec;9(12):1058-1068. doi: 10.1016/j.trecan.2023.08.011. Epub 2023 Sep 12.
Precision oncology requires additional predictive biomarkers for targeted therapy selection. Variant allele frequency (VAF), measuring the proportion of variant alleles within a genomic locus, provides insights into tumor clonality in somatic genomic testing, yielding a strong rationale for targeting dominant cancer cell populations. The prognostic and predictive roles of VAF have been evaluated across different studies. Yet, the absence of validated VAF thresholds and a lack of standardization between sequencing assays currently hampers its clinical utility. Therefore, analytical and clinical validation must be further examined. This Review summarizes the evidence regarding the use of VAF as a predictive biomarker and discusses challenges and opportunities for its clinical implementation as a decision-making tool for targeted therapy selection.
精准肿瘤学需要额外的预测性生物标志物来选择靶向治疗。变异等位基因频率（VAF）衡量基因组位置内变异等位基因的比例，为体细胞基因组检测中的肿瘤克隆性提供了深入了解，为靶向优势癌细胞群体提供了强有力的依据。VAF 的预后和预测作用已在不同研究中得到评估。然而，目前缺乏经过验证的 VAF 阈值，并且测序检测之间缺乏标准化，这限制了其临床应用。因此，必须进一步检查分析和临床验证。本综述总结了 VAF 作为预测性生物标志物的应用证据，并讨论了将其作为靶向治疗选择的决策工具的临床实施所面临的挑战和机遇。
