5-fluorouracil

P2, N=67, Completed, Centre Francois Baclesse | Trial completion date: Mar 2027 --> Nov 2025 | Active, not recruiting --> Completed

P=N/A, N=6, Active, not recruiting, Australasian Gastro-Intestinal Trials Group | Recruiting --> Active, not recruiting | Phase classification: P2 --> PN/A | N=75 --> 6 | Trial completion date: Jun 2025 --> Dec 2027 | Trial primary completion date: Jun 2024 --> Dec 2025

Here, we show that the release of HMGB1 by tumor cells is required for the combinatorial efficacy with TIM-3 blockade observed with paclitaxel, docetaxel, fluorouracil, and irradiation. Instead, STING activation promotes endoplasmic reticulum (ER) stress and lysosomal exocytosis, driving HMGB1 secretion. Thus, non-canonical STING signaling in response to taxanes can promote the efficacy of chemoimmunotherapy.

P2/3, N=290, Recruiting, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) | Not yet recruiting --> Recruiting | Initiation date: Jan 2026 --> Apr 2026

Pivotal trials (MONO, FAST, SPOTLIGHT/GLOW, ILUSTRO) confirmed its monotherapy efficacy and superior PFS/OS when combined with chemotherapy (EOX, mFOLFOX6, CAPOX) in CLDN18.2-positive (≥70% staining), HER2-negative advanced GC/EGJC patients, with manageable safety...However, MMAE's long-term cumulative toxicity, uncertain safety in special populations, and rare severe adverse reactions require real-world validation. This review systematically summarizes zolbetuximab's research progress, providing a reference for clinical application and future studies.

Long-term results from the nITRO trial confirm the activity of perioperative NALIRIFOX in resectable PDAC. Inflammatory, genomic, and pharmacogenomic biomarkers strongly influenced treatment response, surgical eligibility, survival, and toxicity. Biomarker integration could enable more precise patient stratification and guide personalized perioperative strategies in PDAC.

P2/3, N=690, Recruiting, Bristol-Myers Squibb

P1/2, N=42, Not yet recruiting, AstraZeneca AB

P2/3, N=990, Recruiting, Bristol-Myers Squibb

Eight cycles of adjuvant 5-FU plus cisplatin were administered. First recurrence occurred at 32 months, treated with six cycles of 5-FU, carboplatin, and bevacizumab...The enteric immunophenotype and right-sided ovarian dissemination pattern are diagnostic keys. Thorough surgery combined with chemotherapy can achieve long-term survival.

In vitro and in vivo models demonstrate that targeting GPX4 with the ferroptosis activator RSL3 restores chemotherapy sensitivity. These findings identify a novel mechanism of chemoresistance mediated by senEndo-derived GPX4 in extracellular vesicles and highlight the potential of ferroptosis induction, alone or in combination with senolytic agents, to improve 5-Fu/oxaliplatin-based CRC therapies.

Upon 5-fluorouracil (5-FU) treatment, PBX1 overexpression reduced cell viability, while concurrent BCL2L1 knockdown significantly enhanced drug sensitivity...These results support the dual role of PBX1 in simultaneously inhibiting tumor growth while promoting cell survival through the BCL2L1-Bcl-xL axis. This regulatory interaction may influence tumor persistence and therapeutic response in CRC.