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Received — 13 September 2026 ⏭

Multi-Omics-Enabled Precision Strategies for Overcoming CAR-T Therapy Limitations in Gastrointestinal Malignancies

✇Omics in Hepatocellular
By: Ke Su · Zunyuan Tan · Han Li · Kai You · Susu Xiao · Haiqing Chen · Danyang Li · Xin Liu · Xinrui Du · Jiaxin Hu · Kun He · Yantian Xu · Jian Chen · Yunwei Han
10 September 2026 at 18:00

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

✇(Multiomics OR Omics) AND (Pancreatic)
By: Ke Su · Zunyuan Tan · Han Li · Kai You · Susu Xiao · Haiqing Chen · Danyang Li · Xin Liu · Xinrui Du · Jiaxin Hu · Kun He · Yantian Xu · Jian Chen · Yunwei Han
10 September 2026 at 18:00

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

Received — 27 May 2026 ⏭

How Much Thinking is Enough? Quantifying and Understanding Redundancy in LLM Reasoning

✇cs.AI, q-bio.NC updates on arXiv.org
By: Zhiyuan Zhai · Xinkai You · Wenjing Yan · Xin Wang
26 May 2026 at 12:00
arXiv:2605.23926v1 Announce Type: new Abstract: Reasoning-capable large language models solve hard problems by emitting long chains of thought, paying heavily in latency, GPU time, and energy. Casual inspection of their traces reveals extensive reformulation, verification, and circular self-reflection, yet how much of this deliberation is actually necessary has never been measured at scale or explained from first principles. This paper closes both gaps. We formalise reasoning redundancy directly in terms of the reasoning model itself: the redundancy of a correct trace is the largest fraction of its trailing segmented steps that can be truncated while $\pi$, forced to terminate thinking and emit a final answer, still produces the correct answer. A large-scale quantification across four frontier reasoning models and two mathematical benchmarks shows that step-level redundancy is consistently high -- between 61% and 93% across the 8 (model, benchmark) conditions we study, with the median critical prefix equal to a single segmented step in six of the eight conditions -- that the finding is robust to the choice of judge family, and that although $\rho$ decreases with problem difficulty on MATH-500, all four models remain substantially redundant ($\rho \in [46\%, 85\%]$) even on the hardest Level-5 problems. We then prove that this redundancy is a structural consequence of length-agnostic outcome rewards, not a model-specific artefact: under any such reward, no finite expected stopping time is optimal. The result holds regardless of RL algorithm, base model, data distribution, or whether the policy is obtained via RL or distillation; over-thinking is therefore not a bug to be patched in individual models but a structural property of how current reasoning models are trained. Code: https://github.com/zhiyuanZhai20/how-much-thinking-is-enough
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