Table of Contents
Cancer Research Highlights
Genome and Epigenome
This multiethnic study links germline pathogenic variants in BRCA1, BRCA2, and ERCC2 to the development of second primary cancer in breast cancer survivors, providing biological insights and biomarkers to guide patient monitoring.
Metabolism and Chemical Biology
This study demonstrates that the key regulator of glutaminolysis, GLS2, can limit HCC in vivo by promoting ferroptosis through αKG-dependent lipid ROS, which in turn might lay the foundation for a novel therapeutic approach.
GOT2 Silencing Promotes Reprogramming of Glutamine Metabolism and Sensitizes Hepatocellular Carcinoma to Glutaminase Inhibitors
Altered glutamine metabolism induced by GOT2 loss supports HCC growth and metastasis but confers a targetable vulnerability to glutaminase inhibitors.
Molecular Cell Biology
Single-Cell Transcriptome Profiling Reveals Intratumoral Heterogeneity and Molecular Features of Ductal Carcinoma In Situ
Investigation of the molecular features of ductal carcinoma in situ at single cell resolution provides new insights into breast cancer biology and identifies candidate therapeutic targets and diagnostic biomarkers.
And-1 Coordinates with the FANCM Complex to Regulate Fanconi Anemia Signaling and Cisplatin Resistance
This work shows that phosphorylation of And-1 by ATR activates Fanconi anemia signaling at interstrand crosslink–stalled replication forks by recruiting the FANCM/FAAP24 complex, revealing And-1 as a potential therapeutic target in cancer.
This study suggests that cells need to inactivate mTOR to survive nutrient stress, which could explain the rarity of mTOR mutations and the limited clinical activity of mTOR inhibitors in cancer.
Tumor Biology and Immunology
Mapping the Immune Landscape in Metastatic Melanoma Reveals Localized Cell–Cell Interactions That Predict Immunotherapy Response
This study shows that spatial characterization can address the challenge of finding efficient biomarkers, revealing that localization of macrophages and T cells in melanoma predicts patient response to ICI.
Lipid-Associated Macrophages Are Induced by Cancer-Associated Fibroblasts and Mediate Immune Suppression in Breast Cancer
This work identifies a novel lipid–associated macrophage subpopulation with immune suppressive functions, offering new leads for therapeutic interventions in triple-negative breast cancer.
PIM2 Expression Induced by Proinflammatory Macrophages Suppresses Immunotherapy Efficacy in Hepatocellular Carcinoma
Cross-talk between T cells and macrophages regulates cancer cell PIM2 expression to promote cancer aggressiveness, revealing translational approaches to improve response to ICB in hepatocellular carcinoma.
β2-Microglobulin Maintains Glioblastoma Stem Cells and Induces M2-like Polarization of Tumor-Associated Macrophages
β2-microglobulin signaling in glioblastoma cells activates a PI3K/AKT/MYC/TGFβ1 axis that maintains stem cells and induces M2-like macrophage polarization, highlighting potential therapeutic strategies for targeting tumor cells and the immunosuppressive microenvironment in glioblastoma.
This co-clinical trial of combined MEK-CDK4/6 inhibition in RAS mutant colorectal cancer demonstrates therapeutic efficacy in patient-derived xenografts and safety in patients, identifies biomarkers of response, and uncovers targetable mechanisms of resistance.
Alternative Lengthening of Telomeres in Cancer Confers a Vulnerability to Reactivation of p53 Function
This work demonstrates that constitutive activation of ATM in chemotherapy-refractory ALT cancer cells renders them hypersensitive to reactivation of p53 function by APR-246, indicating a potential strategy to overcome therapeutic resistance.
CDK4/6 Inhibition Enhances Oncolytic Virus Efficacy by Potentiating Tumor-Selective Cell Killing and T-cell Activation in Refractory Glioblastoma
This study proposes inhibition of cyclin-dependent kinases as a clinically translatable combinatorial strategy to enhance the efficacy of oncolytic virotherapy in GBM.
Pharmacologic Targeting of TFIIH Suppresses KRAS-Mutant Pancreatic Ductal Adenocarcinoma and Synergizes with TRAIL
This study utilizes functional genetic and pharmacological profiling of KRAS-mutant pancreatic adenocarcinoma to identify therapeutic strategies and finds that TFIIH inhibition synergizes with TRAIL to induce apoptosis in KRAS-driven pancreatic cancer.
Convergence and Technologies
MRI-Based Digital Models Forecast Patient-Specific Treatment Responses to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer
Integrating MRI data with biologically based mathematical modeling successfully predicts breast cancer response to chemotherapy, suggesting digital twins could facilitate a paradigm shift from simply assessing response to predicting and optimizing therapeutic efficacy.