KSR1 Mediates Small Cell Lung Carcinoma Tumor Initiation and Cisplatin Resistance.

ABSTRACT: Small cell lung cancer (SCLC) has a dismal 5-year survival rate of less than 7%, with limited advances in first-line treatment over the past four decades. Tumor-initiating cells (TIC) contribute to resistance and relapse, a major impediment to SCLC treatment. In this study, we identify kinase suppressor of Ras 1 (KSR1), a molecular scaffold for the Raf/MEK/ERK signaling cascade, as a critical regulator of SCLC TIC formation and tumor initiation in vivo. We further show that KSR1 mediates cisplatin resistance in SCLC. Whereas 50% to 70% of control cells show resistance after 6-week exposure to cisplatin, CRISPR/Cas9-mediated KSR1 knockout prevents resistance in >90% of SCLC cells in ASCL1, NeuroD1, and POU2F3 subtypes. KSR1 knockout significantly enhances the ability of cisplatin to decreas

SUBMITTER: Chatterjee D 

PROVIDER: S-EPMC12133430 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature