Combined targeting poly (ADP-ribose) polymerase and receptor tyrosine kinase inhibits ovarian clear cell carcinoma progression through disrupted ribosome biogenesis.

ABSTRACT: OCCC has extremely poor prognosis. ARID1A mutation-related chromatin remodeling errors are key molecular features of OCCC. Dysregulation of receptor tyrosine kinases-related signaling pathways is common in OCCC. Here we show that combination of niraparib and lenvatinib exhibits significant synergistic inhibitory effects against platinum-resistant OCCC cell lines, xenografts, patient-derived tumoroid (PDT) models, and prolonged survival in the platinum-refractory patient-derived xenograft (PDX) model. RNA-sequencing revealed the most differently expressed genes in PDX treated with a combination of niraparib and lenvatinib versus control were in structural ribosomal components. Selected differently expressed ribosomal proteins (RPs: RPS2, RPS5, RPS9, and RPL3) was validated using quantitativ

SUBMITTER: Lin CY 

PROVIDER: S-EPMC12830444 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature