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Endogenous Retroelement Activation by Epigenetic Therapy Reverses the Warburg Effect and Elicits Mitochondrial-Mediated Cancer Cell Death

期刊: CANCER DISCOVERY, 2021; 11 (5)

For millions of years, endogenous retroelements have remained transcriptionally silent within mammalian genomes by epigenetic mechanisms. Modern antic......

Lower Airway Dysbiosis exacerbates Lung cancer

期刊: CANCER DISCOVERY, 2021; 11 (2)

Accumulating evidence supports the impact of the gut microbiota on the clinical efficacy of cancer immunotherapies against extraintestinal tumors, but......

A Burned-Out CD8(+) T-cell Subset Expands in the Tumor Microenvironment and Curbs Cancer Immunotherapy

期刊: CANCER DISCOVERY, 2021; 11 (7)

Specific mechanisms by which tumor-infiltrating lymphocytes (TIL) become dysfunctional remain poorly understood. Here, we employed a two-pronged appro......

CARM1 Inhibition Enables Immunotherapy of Resistant Tumors by Dual Action on Tumor Cells and T Cells

期刊: CANCER DISCOVERY, 2021; 11 (8)

A number of cancer drugs activate innate immune pathways in tumor cells but unfortunately also compromise antitumor immune function. We discovered tha......

SWI/SNF Complex Mutations Promote Thyroid Tumor Progression and Insensitivity to Redifferentiation Therapies

期刊: CANCER DISCOVERY, 2021; 11 (5)

Mutations of subunits of the SWI/SNF chromatin remodeling complexes occur commonly in cancers of different lineages, including advanced thyroid cancer......

The Promising Evolution of Targeted Therapeutic Strategies in Cancer

期刊: CANCER DISCOVERY, 2021; 11 (4)

The upcoming decade of precision medicine for cancer is moving from the translation of specific genetic findings into clinically relevant improvement ......

Simultaneous Inhibition of LSD1 and TGF beta Enables Eradication of Poorly Immunogenic Tumors with Anti-PD-1 Treatment

期刊: CANCER DISCOVERY, 2021; 11 (8)

Epigenetic regulators are a class of promising targets in combination with immune checkpoint inhibitors for cancer treatment, but the impact of the br......

Loss of Optineurin Drives Cancer Immune Evasion via Palmitoylation-Dependent IFNGR1 Lysosomal Sorting and Degradation

期刊: CANCER DISCOVERY, 2021; 11 (7)

Mutations in IFN and MHC signaling genes endow immunotherapy resistance. Patients with colorectal cancer infrequently exhibit IFN and MHC signaling ge......

CRISPR Screening of CAR T Cells and Cancer Stem Cells Reveals Critical Dependencies for Cell-Based Therapies

期刊: CANCER DISCOVERY, 2021; 11 (5)

Glioblastoma (GBM) contains self-renewing GBM stem cells (GSC) potentially amenable to immunologic targeting, but chimeric antigen receptor (CAR) T-ce......

Therapeutically Increasing MHC-I Expression Potentiates Immune Checkpoint Blockade

期刊: CANCER DISCOVERY, 2021; 11 (6)

Immune checkpoint blockade (ICB) therapy revolutionized cancer treatment, but many patients with impaired MHC-I expression remain refractory. Here, we......

An Epigenetic Mechanism Underlying Chromosome 17p Deletion-Driven Tumorigenesis

期刊: CANCER DISCOVERY, 2021; 11 (1)

Chromosome copy-number variations are a hallmark of cancer. Among them, the prevalent chromosome 17p deletions are associated with poor prognosis and ......

TRK xDFG Mutations Trigger a Sensitivity Switch from Type I to II Kinase Inhibitors

期刊: CANCER DISCOVERY, 2021; 11 (1)

On-target resistance to next-generation TRK inhibitors in TRK fusion-positive cancers is largely uncharacterized. In patients with these tumors, we fo......

The Hepatic Microenvironment Uniquely Protects Leukemia Cells through Induction of Growth and Survival Pathways Mediated by LIPG

期刊: CANCER DISCOVERY, 2021; 11 (2)

Due to the disseminated nature of leukemia, malignant cells are exposed to many different tissue microenvironments, including a variety of extramedull......

The RNA m6A Reader YTHDF2 Maintains Oncogene Expression and Is a Targetable Dependency in Glioblastoma Stem Cells

期刊: CANCER DISCOVERY, 2021; 11 (2)

Glioblastoma is a universally lethal cancer driven by glioblastoma stem cells (GSC). Here, we interrogated N-6-methyladenosine (m6A) mRNA modification......

Timed Ang2-Targeted Therapy Identifies the Angiopoietin-Tie Pathway as Key Regulator of Fatal Lymphogenous Metastasis

期刊: CANCER DISCOVERY, 2021; 11 (2)

Recent clinical and preclinical advances have highlighted the existence of a previously hypothesized lymphogenous route of metastasis. However, due to......

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