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Multi-Omics-Enabled Precision Strategies for Overcoming CAR-T Therapy Limitations in Gastrointestinal Malignancies
Biofactors. 2026 Sep-Oct;52(5):e70150. doi: 10.1002/biof.70150.
ABSTRACT
Gastrointestinal malignancies, including gastric cancer, colorectal cancer, hepatocellular carcinoma, and pancreatic ductal adenocarcinoma, remain major causes of cancer-related morbidity and mortality worldwide. Although chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of hematologic malignancies, its efficacy in gastrointestinal solid tumors remains limited by antigen heterogeneity, insufficient trafficking and infiltration, immunosuppressive tumor microenvironments, on-target off-tumor toxicity, and adaptive resistance. In this review, we summarize the current landscape of CAR-T therapy in gastric cancer, colorectal cancer, hepatocellular carcinoma, and pancreatic cancer, with a focus on representative target antigens and emerging biomarker strategies. We further discuss two major categories of biomarkers: target antigen-related biomarkers and conventional dynamic biomarkers, including serum tumor markers, cytokine changes, CAR-T expansion kinetics, and antigen-loss monitoring. In addition, we highlight how single-cell ribonucleic acid sequencing and spatial transcriptomics provide complementary insights into cellular states, immune exhaustion, stromal barriers, and spatially restricted immune exclusion. By integrating these multi-omics approaches with biomarker-guided patient stratification and next-generation CAR-T engineering, gastrointestinal solid tumor CAR-T therapy may evolve from empirical optimization toward mechanism-driven and precision-guided clinical translation.
PMID:42717494 | PMC:PMC13558850 | DOI:10.1002/biof.70150
Multi-Omics-Enabled Precision Strategies for Overcoming CAR-T Therapy Limitations in Gastrointestinal Malignancies
Biofactors. 2026 Sep-Oct;52(5):e70150. doi: 10.1002/biof.70150.
ABSTRACT
Gastrointestinal malignancies, including gastric cancer, colorectal cancer, hepatocellular carcinoma, and pancreatic ductal adenocarcinoma, remain major causes of cancer-related morbidity and mortality worldwide. Although chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of hematologic malignancies, its efficacy in gastrointestinal solid tumors remains limited by antigen heterogeneity, insufficient trafficking and infiltration, immunosuppressive tumor microenvironments, on-target off-tumor toxicity, and adaptive resistance. In this review, we summarize the current landscape of CAR-T therapy in gastric cancer, colorectal cancer, hepatocellular carcinoma, and pancreatic cancer, with a focus on representative target antigens and emerging biomarker strategies. We further discuss two major categories of biomarkers: target antigen-related biomarkers and conventional dynamic biomarkers, including serum tumor markers, cytokine changes, CAR-T expansion kinetics, and antigen-loss monitoring. In addition, we highlight how single-cell ribonucleic acid sequencing and spatial transcriptomics provide complementary insights into cellular states, immune exhaustion, stromal barriers, and spatially restricted immune exclusion. By integrating these multi-omics approaches with biomarker-guided patient stratification and next-generation CAR-T engineering, gastrointestinal solid tumor CAR-T therapy may evolve from empirical optimization toward mechanism-driven and precision-guided clinical translation.
PMID:42717494 | PMC:PMC13558850 | DOI:10.1002/biof.70150
Teclistamab versus lenalidomide-dexamethasone in high-risk smoldering multiple myeloma: a randomized phase 2 trial
Nature Medicine, Published online: 11 September 2026; doi:10.1038/s41591-026-04642-w
In the randomized phase 2 ImmunoPRISM trial, patients with high-risk smoldering multiple myeloma (MM) showed higher rates of complete clinical responses in response to treatment with teclistamab compared with lenalidomide–dexamethasone, although longer follow-up is required to determine durable prevention of progression to MM.Multi-Omics-Enabled Precision Strategies for Overcoming CAR-T Therapy Limitations in Gastrointestinal Malignancies
Biofactors. 2026 Sep-Oct;52(5):e70150. doi: 10.1002/biof.70150.
ABSTRACT
Gastrointestinal malignancies, including gastric cancer, colorectal cancer, hepatocellular carcinoma, and pancreatic ductal adenocarcinoma, remain major causes of cancer-related morbidity and mortality worldwide. Although chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of hematologic malignancies, its efficacy in gastrointestinal solid tumors remains limited by antigen heterogeneity, insufficient trafficking and infiltration, immunosuppressive tumor microenvironments, on-target off-tumor toxicity, and adaptive resistance. In this review, we summarize the current landscape of CAR-T therapy in gastric cancer, colorectal cancer, hepatocellular carcinoma, and pancreatic cancer, with a focus on representative target antigens and emerging biomarker strategies. We further discuss two major categories of biomarkers: target antigen-related biomarkers and conventional dynamic biomarkers, including serum tumor markers, cytokine changes, CAR-T expansion kinetics, and antigen-loss monitoring. In addition, we highlight how single-cell ribonucleic acid sequencing and spatial transcriptomics provide complementary insights into cellular states, immune exhaustion, stromal barriers, and spatially restricted immune exclusion. By integrating these multi-omics approaches with biomarker-guided patient stratification and next-generation CAR-T engineering, gastrointestinal solid tumor CAR-T therapy may evolve from empirical optimization toward mechanism-driven and precision-guided clinical translation.
PMID:42717494 | PMC:PMC13558850 | DOI:10.1002/biof.70150
Multi-Agent Agentic Graph Learning via Structural Signatures
Commensal <i>Nakaseomyces glabratus</i> migrates into prostate tumors to accelerate cancer progression
Nature Cancer, Published online: 09 September 2026; doi:10.1038/s43018-026-01229-9
Lai et al. show that Nakaseomyces glabratus is enriched in fecal and tumor samples of patients with castration-resistant prostate cancer and that administration of the fungus accelerates cancer progression in prostate cancer-bearing castrated mice.Lipotoxicity-induced ER-mitochondrial hypercoupling activates the mtDNA-cGAS-STING-NF-κB axis to drive follicular arrest in metabolically compromised PCOS
Cell Death Discovery, Published online: 08 September 2026; doi:10.1038/s41420-026-03339-w
Lipotoxicity-induced ER-mitochondrial hypercoupling activates the mtDNA-cGAS-STING-NF-κB axis to drive follicular arrest in metabolically compromised PCOSAuthor Correction: A mouse brain stereotaxic topographic atlas with isotropic 1-μm resolution
Nature, Published online: 07 September 2026; doi:10.1038/s41586-026-11094-2
Author Correction: A mouse brain stereotaxic topographic atlas with isotropic 1-μm resolutionMacropinocytosis-mediated recyclable LYTACs (McR-TACs) for receptor-independent protein degradation
Nature Biotechnology, Published online: 31 August 2026; doi:10.1038/s41587-026-03302-1
Recyclable LYTACs induce macropinocytosis to degrade proteins.Beyond Final Answers: Auditing Trajectory-Level Hallucinations in Multi-Agent Industrial Workflows
PANDO: Efficient Multimodal AI Agents via Online Skill Distillation
SimuWoB: Simulating Real-World Mobile Apps for Fast and Faithful GUI Agent Benchmarking
Human-AI Collaboration in Science at Scale: A Global Large-scale Randomized Field Experiment
Subspace-Guided Semantic and Topological Invariant Registration for Annotation-Free Ultrasound Plane Quality Control
Anatomy-Anchored Self-Supervision: Distilling Vision Foundation Models for Invariant Ultrasound Representation
A SAUR gene enhances maize drought resilience by promoting silk elongation
Nature, Published online: 20 May 2026; doi:10.1038/s41586-026-10566-9
The Small Auxin Up RNA (SAUR) protein ZmSAUR72 in maize (Zea mays) promotes silk growth via regulation of H+-ATPase activity, and is a key determinant of the anthesis-silking interval and thus resilience to drought.Linear RAG scanning mediates editing of Igκ variable region repertoires
Nature, Published online: 15 April 2026; doi:10.1038/s41586-026-10362-5
Studies explaining the secondary Igk recombination mechanism are described and Cer/Sis deletion and/or displacement is implicated as a developmental switch converting the rearrangement mechanisms from two-loop-based diffusional primary Igk into one-loop-based linear scanning secondary mechanisms.Deep-sea mining mustn’t go ahead until there are baseline data
Nature, Published online: 14 April 2026; doi:10.1038/d41586-026-01215-2
Deep-sea mining mustn’t go ahead until there are baseline data