Gastrointestinal Cancer

A total of 174 elderly patients (≥60 years) scheduled for elective radical gastrointestinal cancer surgery will be randomized in a 1:1 ratio to receive either two ultrasound-guided SGBs (one on the afternoon before surgery and one 30 min before anesthesia induction) with 0.375% ropivacaine (3-5 mL each) or a sham block with normal saline (3-5 mL)...This study will provide preliminary evidence on the feasibility and efficacy of SGB as a targeted intervention for high-risk older surgical oncology patients, while acknowledging that the assumed effect size may be optimistic. https://www.chictr.org.cn/showproj.html?proj=302103, identifier: ChiCTR2600118223.

The anti-Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) monoclonal antibody ramucirumab was the first antiangiogenic agent approved for HER2-negative metastatic gastric adenocarcinomas and remains a standard second-line treatment either alone or in combination with paclitaxel. Other VEGFR-targeting agents, such as the tyrosine kinase inhibitors (TKI) regorafenib and apatinib, have failed to demonstrate any survival benefit in the first-line settings, while providing modest improvements in pretreated patients, even when combined with Immune Checkpoint Inhibitors (ICI)...Although several biomarker candidates have been explored, reliable predictors are still awaited. This review summarizes current evidence and explores the future of antiangiogenic agents in gastric cancers.

Mechanistically, ATG4B inhibition by compound a25 disrupted autophagic homeostasis, leading to impaired autophagy flux and enhanced cell death. Our study identifies compound a25 as a novel ATG4B inhibitor with compelling preclinical efficacy against ESCC, providing a strategic foundation for targeting pro-tumor autophagy in gastrointestinal cancers.

Although HER2-targeted therapies, such as trastuzumab deruxtecan, have shown promising results in HER2-positive bladder cancer, optimal immunohistochemistry (IHC) scoring criteria for urothelial carcinoma remain unclear...Upper GI and breast scoring criteria yield divergent scores in a significant subset of urothelial carcinomas, potentially affecting eligibility for targeted therapy. Associations with histologic subtype and metastatic site support disease-specific diagnostic and therapeutic strategies.

P1, N=16, Not yet recruiting, Sichuan Baili Pharmaceutical Co., Ltd.

A high-affinity anti-CDH17 monoclonal antibody (TAVO307) was generated and conjugated with auristatin-derived cytotoxic payloads to obtain CDH17-directed antibody-drug conjugates (ADCs)...Both CDH17-targeted ADCs and γδ TCEs demonstrated promising potency and efficacy to control GI cancers. They could offer complementary therapeutic options that could be used in combination therapy.

P1/2, N=186, Recruiting, Zhejiang Doer Biologics Co., Ltd. | Trial completion date: Jun 2026 --> Jun 2027 | Trial primary completion date: Apr 2026 --> Apr 2027

P=N/A, N=1500, Not yet recruiting, Hunan Cancer Hospital

P2, N=30, Completed, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University | Not yet recruiting --> Completed | Trial completion date: Aug 2024 --> Sep 2025 | Trial primary completion date: Mar 2024 --> Sep 2025

P=N/A, N=340, Recruiting, Baylor College of Medicine | Trial completion date: Jun 2026 --> Jun 2027 | Trial primary completion date: May 2026 --> May 2027

DDR mutational landscapes function as context-dependent biomarkers of ICB efficacy. A DDR-based machine learning model predicts ICB outcomes beyond mutation burden, supporting a translational framework for context-aware biomarker development in precision oncology.

pylori in the stomach, F. nucleatum in the colon) shape the prevalence of each archetype. By elucidating the molecular circuits and environmental dependencies underlying these spatially encoded resistance programs, we articulate a translational imperative: archetype-guided spatial biomarkers and targeted microenvironment-remodeling strategies provide the most viable framework to extend durable immunotherapeutic benefit to the historically refractory MSS/pMMR gastrointestinal cancer population.