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The landmark analysis of 100,000 patients in the AACR GENIE cohort illustrates use of this data set to predict clinical trial matching, uncover mechanisms of drug resistance, characterize rare cancers, and inform future whole-genome studies of cancer types without drivers detected by gene panels.

Alpelisib monotherapy was efficacious in patients with PIK3CA mutant hormone receptor–positive breast cancer, with baseline ESR1 mutations and on-treatment circulating tumor DNA dynamics defining patients more likely to benefit.

Integrative multiomic profiling of highrisk prostate cancer specimens in a neoadjuvant clinical trial identified an acquired dependency on the circadian regulator ARNTL upon hormonal intervention.

Single-cell analyses demonstrate diverse fate potentials within CAR T-cell products and identify an unexpected surface phenotype (TIGIT+, CD62Llo, CD27) distinguishing cells that become functional effectors within patients.

PRC2 inactivation in malignant peripheral nerve sheath tumors and melanoma potentiates DNMT1 inhibitor–mediated derepression of retrotransposons, which leads to increased immune pathway signaling and cell death through the double-stranded RNA sensor PKR.

Both IL-1β and TNFα were found to induce IL-8 transcription and secretion in multiple cancer types in a manner that can be drugged using clinically available neutralizing agents.

RNF113A methylation by SMYD3 improves alkylation damage response and impairs small cell lung cancer sensitivity to alkylation-based chemotherapy.

NCOA4-mediated selective autophagy of ferritin (“ferritinophagy”) is upregulated in pancreatic adenocarcinoma to support iron metabolism for tumor progression, thereby representing a new therapeutic target.

Interplay between MiT/TFE and c-MYC transcription factors fine-tune autophagy and lysosome biogenesis to promote increased ferritin degradation and iron supply, which fuel increased mitochondrial respiration during adaptation to RAS–MAPK pathway inhibition.

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Research Watch

Pediatric Cancer
Clinical Trials
Pancreatic Cancer
Structural Biology
Mitochondria
Immunotherapy
Drug Combinations
Stem Cells
Hepatocellular Carcinoma
Genome-wide Association Studies
Metabolism
Immunology
Prostate Cancer
Drug Discovery
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