Table of Contents
Cancer Research Highlights
Controversy and Consensus
Genome and Epigenome
This study identifies cancer-driving mutations in histones as sites of PARP1–mediated ADP-ribosylation in breast and ovarian cancers, providing a molecular pathway by which cancers may subvert the growth-regulating effects of PARP1.
Bimodal Gene Expression in Patients with Cancer Provides Interpretable Biomarkers for Drug Sensitivity
A new machine learning pipeline exploits the bimodality of gene expression to provide a reliable set of candidate predictive biomarkers with a high potential for clinical translatability.
Metabolism and Chemical Biology
Targeting BCAT1 Combined with α-Ketoglutarate Triggers Metabolic Synthetic Lethality in Glioblastoma
Metabolic synthetic lethal screening in IDHWT glioblastoma defines a vulnerability to ΑΚG following BCAT1 loss, uncovering a therapeutic strategy to improve glioblastoma treatment.
Differential expression of PKM1 and PKM2 impacts prostate tumorigenesis and suggests a potential therapeutic vulnerability in prostate cancer.
Hypoxia-Reoxygenation Couples 3βHSD1 Enzyme and Cofactor Upregulation to Facilitate Androgen Biosynthesis and Hormone Therapy Resistance in Prostate Cancer
Hypoxia followed by reoxygenation in prostate cancer drives androgen deprivation therapy resistance via increasing the rate-limiting enzyme and cofactors for androgen synthesis, revealing HIF2α as a therapeutic target to subvert resistance.
Molecular Cell Biology
This study identifies the mitochondrial micropeptide STMP1 as a regulator of metastasis that promotes mitochondrial fission and tumor cell migration via DRP1 and MYH9.
Anti-HIV Drug Elvitegravir Suppresses Cancer Metastasis via Increased Proteasomal Degradation of m6A Methyltransferase METTL3
This study finds that METTL3 promotes cancer metastasis by activating EGR1/Snail signaling in an m6A-dependent manner, revealing vulnerability to METTL3 blockade in esophageal squamous cell carcinoma.
Tumor Biology and Immunology
Transcriptional Repression by FoxM1 Suppresses Tumor Differentiation and Promotes Metastasis of Breast Cancer
This work provides new insights into how the interaction between FoxM1 and Rb facilitates the evolution of metastatic breast cancer cells by altering the transcriptome.
Claudin-12 Deficiency Inhibits Tumor Growth by Impairing Transendothelial Migration of Myeloid-Derived Suppressor Cells
Claudin-12–mediated homotypic interactions are critical for migration of myeloid-derived suppressor cells across vascular walls into tumor tissue, providing a potential therapeutic approach to overcome cancer immunosuppression.
Convergence and Technologies
Analysis of >700 RAS structures helps define an expanded landscape of active, inactive, and druggable RAS conformations, the structural impact of common RAS mutations, and previously uncharacterized RAS inhibitor–binding modes.
Editor's Note: Identification of Src-Specific Phosphorylation Site on Focal Adhesion Kinase: Dissection of the Role of Src SH2 and Catalytic Functions and Their Consequences for Tumor Cell Behavior