KDM6B inhibition enhances chemotherapeutic response in small cell lung cancer via epigenetic regulation of apoptosis and ferroptosis.

ABSTRACT:

Background

Small cell lung cancer (SCLC) is a highly aggressive malignancy characterized by rapid progression and the frequent emergence of resistance to standard chemotherapeutic agents such as cisplatin (DDP) and etoposide (VP16), resulting in poor clinical outcomes.

Methods and results

To elucidate mechanisms underlying chemoresistance, we conducted a genome-wide CRISPR/Cas9 knockout screen, which identified the histone demethylase KDM6B as a critical mediator of drug resistance in SCLC. Genetic silencing of KDM6B significantly reduced IC₅₀ values of DDP and VP16, particularly in H69-AR cells, and enhanced chemotherapy-induced apoptosis. Consistently, pharmacological inhibition of KDM6B using the dual KDM6A/B inhibitor Gskj1 markedly potentiated the effects of DDP and VP1

SUBMITTER: Wang Z 

PROVIDER: S-EPMC12659317 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature