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Ruppin and colleagues overview recent research on the use of AI frameworks in precision oncology, describe ten hallmarks of their contributions across cancer detection, therapy optimization and treatment discovery, and discuss key challenges in clinical implementation
By integrating single-cell RNA and physically interacting cell sequencing analysis, here Cohen and colleagues report that neutrophils are enriched in physical crosstalk with breast tumor cells, promoting cancer aggressiveness.
Traditional antibody–toxin conjugates (ATCs) are designed to target and destroy cancer cells. We present an ATC that acts on innate immune cells to promote tumor-cell phagocytosis and facilitate the translocation of tumor-derived antigens from phagolysosomes into the cytosol, where antigen cross-presentation and immune activation occur.
Bilen et al. perform a phase 2 single-arm clinical trial of neoadjuvant cabozantinib in patients with locally advanced nonmetastatic clear cell renal cell carcinoma, assess efficacy and find antitumor CD8+ T cell response activation upon treatment.
Schrank et al. report the design and characterization of an antibody–toxin conjugate targeting CD47, promoting anti-tumor immunity in preclinical cancer models.
Although enhancing the GTPase activity of KRAS is an attractive approach to inhibit constitutively active, GTP-bound mutant KRAS, so far this has not been achieved. Now, a RAS inhibitor thought to act by preventing engagement of downstream effectors is shown to also reactivate cycling to the inactive GDP-bound state.
Marabelle et al. present updated data from the KEYNOTE-158 trial after ~4.5 years of follow-up, reporting an overall response rate of 34% and a median overall survival of 19.8 months in participants with MSI-H/MMR advanced noncolorectal solid tumors.
BRCA1 mediates homology-directed repair (HDR) of double-strand DNA breaks, explaining the sensitivity of BRCA1-deficient cancers to therapies that block DNA repair, while mutations that restore HDR cause therapy resistance. Research now reveals a mechanistically distinct vulnerability of BRCA1-deficient cancer cells to gap-inducing DNA nicks.
Bando et al. perform a phase II trial of atezolizumab monotherapy following platinum-based definitive chemoradiotherapy in patients with unresectable locally advanced esophageal squamous cell carcinoma and report a complete response rate of 42%.
The tumor microenvironment has a crucial role in tumor progression and metastasis formation. A single-cell analysis now compares the microenvironments of primary tumor and peritoneal metastases in colorectal cancer and shows that neutrophils and fibroblasts contribute to the unique biology of peritoneal metastatic disease.
Li et al. show through single-cell and functional data that tumor microenvironment remodeling promotes peritoneal metastasis of colorectal cancer through microbiome dysbiosis, neutrophil recruitment and mesenchymal transition of mesothelial cells.
McGaha and colleagues review recent research on the metabolic programs of tumor-associated macrophages across cancer types and discuss their implications on potential therapeutic vulnerabilities.
Yang and colleagues present a small-molecule inhibitor for ADAR1 and show that its use is therapeutically beneficial in the context of prostate cancer.
Fan and colleagues show that FLASH radiation promotes proinflammatory polarization of tumor-associated macrophages, which in turn increases T cell influx in medulloblastoma and synergizes with CAR-T cell therapy.
Lillian Siu is director of the Phase I Clinical Trials Program, codirector of the Robert and Maggie Bras and Family Drug Development Program, clinical lead for the Tumor Immunotherapy Program, and the BMO Chair in Precision Cancer Genomics at the Princess Margaret Cancer Centre, University Health Network in Toronto, Canada. She is also a professor of medicine at the University of Toronto and AACR President-Elect 2024–2025. We caught up with her to discuss her career and developments in the clinical oncology field.
To mark the fifth anniversary of Nature Cancer, we launch a Series of Reviews and opinion pieces that will run throughout this year. We take this opportunity to reflect on the journal’s first five years and what comes next.
Five experts share their thoughts on key areas of focus in multidisciplinary cancer research for the upcoming years. They discuss the research approaches, tools, technologies, collaborations and way of thinking the lab of the future should integrate.
