Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.
Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
Cancer Discov. 2024 Jan 12;14(1):49-65. doi: 10.1158/2159-8290.CD-23-0467.
There is a continuing debate about the proportion of cancer patients that benefit from precision oncology, attributable in part to conflicting views as to which molecular alterations are clinically actionable. To quantify the expansion of clinical actionability since 2017, we annotated 47,271 solid tumors sequenced with the MSK-IMPACT clinical assay using two temporally distinct versions of the OncoKB knowledge base deployed 5 years apart. Between 2017 and 2022, we observed an increase from 8.9% to 31.6% in the fraction of tumors harboring a standard care (level 1 or 2) predictive biomarker of therapy response and an almost halving of tumors carrying nonactionable drivers (44.2% to 22.8%). In tumors with limited or no clinical actionability, TP53 (43.2%), KRAS (19.2%), and CDKN2A (12.2%) were the most frequently altered genes.
Although clear progress has been made in expanding the availability of precision oncology-based treatment paradigms, our results suggest a continued unmet need for innovative therapeutic strategies, particularly for cancers with currently undruggable oncogenic drivers. See related commentary by Horak and Fröhling, p. 18. This article is featured in Selected Articles from This Issue, p. 5.
关于癌症患者中有多少人受益于精准肿瘤学，一直存在争议，部分原因是对于哪些分子改变具有临床可操作性存在不同意见。为了量化自 2017 年以来临床可操作性的扩展，我们使用 OncoKB 知识库的两个时间上不同的版本对使用 MSK-IMPACT 临床检测方法测序的 47271 个实体瘤进行了注释，这两个版本的知识库相隔 5 年。在 2017 年至 2022 年期间，我们观察到具有标准治疗（1 级或 2 级）治疗反应预测生物标志物的肿瘤比例从 8.9%增加到 31.6%，而具有非可操作性驱动因素的肿瘤比例几乎减半（从 44.2%降至 22.8%）。在临床可操作性有限或没有的肿瘤中，TP53（43.2%）、KRAS（19.2%）和 CDKN2A（12.2%）是最常改变的基因。
尽管在扩大基于精准肿瘤学的治疗方案的可及性方面已经取得了明显的进展，但我们的结果表明，特别是对于目前无法治疗的致癌驱动因素的癌症，仍然需要创新的治疗策略。见 Horak 和 Fröhling 的相关评论，第 18 页。本文选自本期精选文章，第 5 页。
