NF1/2 mutations predict favorable benefit from immune checkpoint inhibitor-based therapies over VEGFR/mTOR inhibitors in clear cell renal cell carcinoma.

ABSTRACT: Immune checkpoint inhibitors (ICIs) have revolutionized the management of advanced clear cell renal cell carcinoma (ccRCC), but the biomarkers predicting benefits from ICI-based therapies over conventional VEGFR/mTOR inhibitors remain incompletely elucidated. In this study, we analyzed clinical, mutational, and/or transcriptomic data of multiple cohorts, including five clinical trials (JAVELIN Renal 101 [n = 885], IMmotion151 [n = 715], and CheckMate-009/010/025 [n = 1006]), two prognostic cohorts (TCGA-KIRC, n = 537; ICGC, n = 475). Pharmacogenomic analysis was conducted using the cancer cell line encyclopedia (CCLE) database. Our results revealed that only NF1/2 mutations exhibited a consistent relationship with benefits from ICI-based therapies over VEGFR/mTOR inhibitors among all the c

SUBMITTER: Sun Y 

PROVIDER: S-EPMC12847219 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature