SCH 1473759 / Merck (MSD) - LARVOL DELTA

Epigenome-wide DNA methylation analysis of small cell lung cancer cell lines suggests potential chemotherapy targets. (PubMed, Clin Epigenetics) - "Multiple associations indicate potential epigenetic mechanisms affecting SCLC response to chemotherapy and suggest targets for combination therapies. While many correlations were not specific to SCLC lineages, several lineage markers were associated with specific agents."

IO Biomarker • Journal • Preclinical • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • Thoracic Cancer • ATR • EPAS1 • EPHA2 • EZH2 • SLFN11 • STING • YAP1

Associations of epigenome-wide DNA methylation patterns with chemosensitivity and chemoresistance of small cell lung cancer cell lines (AACR-NCI-EORTC 2019) - "Increased methylation and low expression of TREX1 were associated with SCLC cell line sensitivity to multiple Aurora kinase inhibitors AZD-1152, SCH-1473759, SNS-314, and TAK-901, as well as to the CDK inhibitor R-547, Vertex ATR inhibitor Cpd 45, and the mitotic spindle disruptor vinorelbine...Among other examples, EPAS1 (HIF2A) was associated with several Aurora kinase inhibitors, the PLK1 inhibitor GSK-461364, and the Bcl-2 inhibitor ABT-737...IGFBP5, which is expressed in the tuft cell-like SCLC subtype, was associated with the mTOR inhibitor INK-128...Methylation and expression of YAP1, a SCLC lineage driver regulating the Hippo pathway, were correlated with the MTOR inhibitor rapamycin...The 5’ UTR region of the epigenetic modifier EZH2 was associated with Aurora kinase inhibitors and the FGFR inhibitor BGJ-398. These and multiple other associations identified in this study provide a novel understanding of epigenetic mechanisms which may modulate SCLC response to..."

IO Biomarker • Preclinical • EPAS1 • EPHA2 • EZH2