Issues
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Cover Image
Cover Image
Although immunotherapy has revolutionized the way lung cancer patients are treated, most of them will not respond. Many of the mechanisms of resistance remain obscure, but recent work has started to shed light on the role of tumor suppressor genes (TSG) in shaping the tumor microenvironment (TME). PTEN is a TSG frequently mutated in lung squamous carcinoma. PTEN loss of function causes immunotherapy resistance by increasing the number of T regulatory cells and elevating expression of immunosuppressive factors (TGFβ, CXCL10) to the TME. Therapeutic approaches based on TLR agonists and TGFβ inhibition can induce a potent antitumor response in PTEN-deficient tumors, leading to tumor rejection and immunological memory. The image illustrates that, by illuminating key molecular mechanisms of resistance, appropriate treatments can be identified to sensitize tumors to immunotherapy. For details, see article by Exposito and colleagues on page 2513. - PDF Icon PDF LinkTable of Contents
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Cancer Research
Table of Contents
Obituary
In the Spotlight
Review
The mTOR Signaling Pathway Interacts with the ER Stress Response and the Unfolded Protein Response in Cancer
Priority Reports
Oxidative Phosphorylation Fueled by Fatty Acid Oxidation Sensitizes Leukemic Stem Cells to Cold
Mitochondrial metabolism fueled by FAO alters the membrane composition and introduces membrane fragility upon cold exposure in OxPhos-driven AML and in LSCs.
Characterizing Evolutionary Dynamics Reveals Strategies to Exhaust the Spectrum of Subclonal Resistance in EGFR-Mutant Lung Cancer
Unraveling the trajectories of preexisting resistant and drug-tolerant persister cells facilitates the rational design of multidrug combination or sequential therapies, presenting an approach to explore for treating EGFR-mutant lung cancer.
Cancer Biology
Deficiency of the Polycomb Protein RYBP and TET Methylcytosine Oxidases Promotes Extensive CpG Island Hypermethylation and Malignant Transformation
Dysfunction of the Polycomb component RYBP in combination with loss of 5-methylcytosine oxidases promotes widespread hypermethylation of CpG islands in bronchial cells and induces tumorigenesis, resembling changes seen in human lung tumors.
Hypoxia-Responsive lncRNA AC115619 Encodes a Micropeptide That Suppresses m6A Modifications and Hepatocellular Carcinoma Progression
A micropeptide encoded by lncRNA AC115619 impedes formation of the m6A methylation complex to lower m6A levels and reduce the growth of hepatocellular carcinoma.
Cancer Immunology
PTEN Loss Confers Resistance to Anti–PD-1 Therapy in Non–Small Cell Lung Cancer by Increasing Tumor Infiltration of Regulatory T Cells
PTEN loss leads to development of an immunosuppressive microenvironment in lung cancer that confers resistance to anti–PD-1 therapy, which can be overcome by targeting PTEN loss–mediated immunosuppression.
PP2Ac Deficiency Enhances Tumor Immunogenicity by Activating STING–Type I Interferon Signaling in Glioblastoma
PP2Ac deficiency promotes cGAS–STING signaling in glioma to induce a tumor-suppressive immune microenvironment, highlighting PP2Ac as a potential therapeutic target to enhance tumor immunogenicity and improve response to immunotherapy.
Therapeutic Development and Chemical Biology
Proteasome Inhibition Sensitizes Liposarcoma to MDM2 Inhibition with Nutlin-3 by Activating the ATF4/CHOP Stress Response Pathway
Targeting the proteasome in combination with MDM2 inhibition activates the ATF4/CHOP stress response axis to induce apoptosis in liposarcoma, providing a potential therapeutic approach for the most common soft–tissue sarcoma.
Translational Cancer Biology
Functional and Clinical Characterization of Variants of Uncertain Significance Identifies a Hotspot for Inactivating Missense Variants in RAD51C
Functional analysis of the impact of a large number of missense variants on RAD51C function provides insight into RAD51C activity and information for classification of the cancer relevance of RAD51C variants.
A Genetic Locus within the FMN1/GREM1 Gene Region Interacts with Body Mass Index in Colorectal Cancer Risk
This gene-environment interaction analysis revealed a genetic locus in FMN1/GREM1 that interacts with body mass index in colorectal cancer risk, suggesting potential implications for precision prevention strategies.
Cancer Landscapes
Oncogenic Transformation Drives DNA Methylation Loss and Transcriptional Activation at Transposable Element Loci
Analysis of epigenetic and transcriptional changes in a transformation model reveals that transposable element expression and methylation are dysregulated during oncogenic transformation.
Convergence Science
Profiling the Somatic Mutational Landscape of Breast Tumors from Hispanic/Latina Women Reveals Conserved and Unique Characteristics
Comprehensive characterization of genomic and transcriptomic alterations in breast tumors from Hispanic/Latina patients reveals distinct genetic alterations and signatures, demonstrating the importance of inclusive studies to ensure equitable care for patients.
BRCA1 Insufficiency Induces a Hypersialylated Acidic Tumor Microenvironment That Promotes Metastasis and Immunotherapy Resistance
BRCA1 deficiency generates an acidic microenvironment to promote cancer metastasis and immunotherapy resistance that can be reversed using a sialyltransferase inhibitor.
Journal Archive
Cancer Research
(1941-Present; volumes 1-current)Published twice monthly since 1987. From 1941-1986, published monthly.
(ISSN 0008-5472)
The American Journal of Cancer
(1931-1940; volumes 15-40)Published quarterly in 1931, bimonthly in 1932, and monthly from 1933 to 1940. The journal changed title to Cancer Research in 1941.
(ISSN 0099-7374)
The Journal of Cancer Research
(1916-1930); volumes 1-14)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.
(ISSN 0099-7013)
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