In This Issue
In the Spotlight
Science in Society
Molecular Characterization of Endometrial Carcinomas in Black and White Patients Reveals Disparate Drivers with Therapeutic Implications
Clinical panel sequencing analysis of endometrial cancers (EC) identified differences in the prevalence of histologic types, molecular subtypes, and genetic alterations by self-identified race/genetic ancestry, providing insights into EC disparities.
Clinical Efficacy of ONC201 in H3K27M-Mutant Diffuse Midline Gliomas Is Driven by Disruption of Integrated Metabolic and Epigenetic Pathways
Combined clinical, radiographic, and molecular analyses demonstrate the efficacy of ONC201 in H3K27M-mutant diffuse midline glioma, as ONC201 was shown to disrupt integrated metabolic and epigenetic pathways and reverse pathognomonic H3K27me3 reduction.
Neoadjuvant Durvalumab Alone or Combined with Novel Immuno-Oncology Agents in Resectable Lung Cancer: The Phase II NeoCOAST Platform Trial
NeoCOAST, the first neoadjuvant platform trial of novel immuno-oncology combinations, demonstrates that combined therapies improve responses and immunologic cell activation compared to durvalumab (anti–PD-L1) monotherapy in resectable non–small cell lung cancer.
MRTX1719 Is an MTA-Cooperative PRMT5 Inhibitor That Exhibits Synthetic Lethality in Preclinical Models and Patients with MTAP-Deleted Cancer
Targeting the PRMT5/MTA complex selectively inhibits growth of MTAP-deleted preclinical cancer models and demonstrates preliminary clinical activity in MTAP-deleted cancers.
STX-478, a Mutant-Selective, Allosteric PI3Kα Inhibitor Spares Metabolic Dysfunction and Improves Therapeutic Response in PI3Kα-Mutant Xenografts
The preclinical profile of STX-478, a mutant-selective, allosteric PI3Kα inhibitor, demonstrates its potential to expand the limited therapeutic window of approved inhibitors and significantly improve outcomes in patients with PI3Kα-mutant cancers.
BCL2 Inhibition Reveals a Dendritic Cell–Specific Immune Checkpoint That Controls Tumor Immunosurveillance
BCL2 inhibition in type 1 conventional dendritic cells (cDC1) activates the cGAS/STING/type 1 IFN pathway and exerts cDC1-dependent, T cell–mediated anticancer effects, unveiling BCL2 as an endogenous checkpoint of cDC1.
Transposable Elements Are Co-opted as Oncogenic Regulatory Elements by Lineage-Specific Transcription Factors in Prostate Cancer
Oncogenesis arises from hijacking a subset of transposable elements active in pluripotent stem cells into regulatory elements for lineage-specific transcription factors, such as the androgen receptor in prostate cancer.