Cover ImageMacroscopic liver metastases of colorectal cancer demonstrate heterogeneous expression of intestinal stem cell markers, while micrometastases are devoid of stem cell markers. The cover image shows a spontaneous liver macrometastasis of a colorectal cancer organoid that was orthotopically transplanted in a mouse. Patient-derived colorectal cancer organoids were equipped with the stem cell ASCL2 reporter STAR prior to transplantation, which leads to ASCL2-controlled nuclear expression of a red fluorophore. Cells of human origin were identified by immunohistochemistry against human CEA (green), and sides were counterstained with DAPI (blue). For details, see the article by Heinz and colleagues on page 1953.Close Modal
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Cancer Research (1941-Present; volumes 1-current)(ISSN 0008-5472) Published twice monthly since 1987. From 1941-1986, published monthly.
The American Journal of Cancer (1931-1940; volumes 15-40)(ISSN 0099-7374) Published quarterly in 1931, bimonthly in 1932, and monthly from 1933 to 1940. The journal changed title to Cancer Research in 1941.
The Journal of Cancer Research (1916-1930); volumes 1-14)(ISSN 0099-7013) Published quarterly from 1916 through 1930 (publication was suspended from November 1922 to March 1924). The journal changed title to The American Journal of Cancer in 1931.
Table of Contents
Pathophysiologic and Pharmacologic Considerations to Improve the Design and Application of Antibody–Drug Conjugates
Cancer Research Highlights
Plasticity Enables Cooperation among Heterogeneous Cancer Cell Populations to Support Metastatic Fitness
Genome and Epigenome
M6A RNA Methylation Regulates Histone Ubiquitination to Support Cancer Growth and Progression
RNA demethylase ALKBH5 upregulates USP22 and RNF40 to inhibit histone H2A ubiquitination and induces expression of key replication and DNA repair–associated genes, driving osteosarcoma progression.
Metabolism and Chemical Biology
Bcl-xL Enforces a Slow-Cycling State Necessary for Survival in the Nutrient-Deprived Microenvironment of Pancreatic Cancer
The majority of pancreatic cancer cells inhabit nutrient- and oxygen-poor tumor regions and require Bcl-xL for their survival, providing a compelling antitumor metabolic strategy.
Molecular Cell Biology
Suppression of Endothelial Cell FAK Expression Reduces Pancreatic Ductal Adenocarcinoma Metastasis after Gemcitabine Treatment
These findings establish the potential utility of combinatorial endothelial cell FAK targeting together with gemcitabine in future clinical applications to control metastasis in patients with pancreatic ductal adenocarcinoma.
Differential Gain-of-Function Activity of Three p53 Hotspot Mutants In Vivo
p53 hotspot mutants inhibit wild-type p53 similarly but differ in their GOF activities, with stronger tumor-promoting activity in contact mutants and distinct protein partners of each mutant driving tumorigenesis and metastasis.
RNA Helicase DHX37 Facilitates Liver Cancer Progression by Cooperating with PLRG1 to Drive Superenhancer-Mediated Transcription of Cyclin D1
This work characterizes a novel mechanism of superenhancer-driven cyclin D1 upregulation by DHX37 and PLRG1, implicating this pathway as a potential therapeutic target in hepatocellular carcinoma.
Tumor Biology and Immunology
Liver Colonization by Colorectal Cancer Metastases Requires YAP-Controlled Plasticity at the Micrometastatic Stage
Characterization of the cell type dynamics, composition, and transcriptome of early colorectal cancer liver metastases reveals that failure to establish cellular heterogeneity through YAP-controlled epithelial self-organization prohibits the outgrowth of micrometastases.
Carbon Monoxide Activates PERK-Regulated Autophagy to Induce Immunometabolic Reprogramming and Boost Antitumor T-cell Function
Transient activation of ER stress with carbon monoxide drives mitochondrial biogenesis and protective autophagy that elicits superior antitumor T-cell function, revealing an approach to improving adoptive cell efficacy therapy.
Thymosin α-1 Reverses M2 Polarization of Tumor-Associated Macrophages during Efferocytosis
Thymosin α-1 improves the curative effect of chemotherapy by reversing efferocytosis-induced M2 polarization of macrophages via activation of a TLR7/SHIP1 axis.
HSP90 Mediates IFNγ-Induced Adaptive Resistance to Anti-PD-1 Immunotherapy
This study reveals an HSP90-centric, iron-modulated mechanism that confers immunosuppression, offering potential therapeutic targets for interfering with acquired resistance to the most prevalent anticancer immunotherapies.
Loss of H3K27 Trimethylation Promotes Radiotherapy Resistance in Medulloblastoma and Induces an Actionable Vulnerability to BET Inhibition
This study demonstrates a novel epigenetic mechanism of radiation resistance in medulloblastoma and identifies a therapeutic approach to improve outcomes in these patients.
Convergence and Technologies
Chemotherapy-Induced Collagen IV Drives Cancer Cell Motility through Activation of Src and Focal Adhesion Kinase
Cytotoxic chemotherapy induces significant changes in the composition of tumor ECM, inducing a more invasive and aggressive phenotype in residual tumor cells following chemotherapy.