gemcitabine

P2, N=32, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Mar 2026 --> Mar 2027 | Trial primary completion date: Mar 2026 --> Mar 2027

P1, N=36, Recruiting, University of California, San Diego | Trial primary completion date: Jun 2027 --> Dec 2027

P1, N=172, Recruiting, K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc | Trial completion date: Feb 2027 --> Jun 2028 | Trial primary completion date: Dec 2024 --> Jun 2028

P2, N=120, Recruiting, ALX Oncology Inc. | Phase classification: P1/2 --> P2 | N=80 --> 120 | Trial completion date: Dec 2027 --> Dec 2028 | Trial primary completion date: Jun 2027 --> Dec 2027

P2, N=47, Completed, Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | Recruiting --> Completed | N=90 --> 47 | Trial completion date: May 2024 --> May 2025 | Trial primary completion date: Oct 2023 --> May 2025

P3, N=398, Recruiting, Suzhou Suncadia Biopharmaceuticals Co., Ltd. | Not yet recruiting --> Recruiting

P1/2, N=117, Active, not recruiting, Cantargia AB | Trial primary completion date: Jun 2025 --> Apr 2026

Interleukin-18 (IL-18) is a pro-inflammatory cytokine, and higher IL-18 expression in pancreatic tumors is associated with poor prognosis. On the other hand, the release of active IL-18 was not observed with gemcitabine. These findings suggest that a low-nutrient tumor microenvironment and 5-FU therapy can promote caspase-8-dependent pyroptotic cell death with IL-18 activation, potentially contributing to chronic inflammation in pancreatic tumors.

This study shows that UNC569 potently suppresses PDAC cell proliferation and clonogenic growth, inhibits migration and invasion by attenuating epithelial-mesenchymal transition, and enhances the sensitivity of PDAC cells to Gemcitabine while promoting apoptosis. Mechanistically, UNC569 induces DNA damage-mediated G2/M phase arrest and activates JNK/p38 mitogen-activated protein kinase-dependent apoptotic signaling. Collectively, these results establish MerTK as a promising therapeutic target in PDAC and highlight the translational potential of UNC569 as a dual-pathway inhibitor for PDAC treatment.

Notably, CALB2 knockdown significantly sensitized CCA tumors to gemcitabine plus radiotherapy, an effect attenuated by KRT7 overexpression. These findings define a novel H3K4 methylation/CALB2/calcium/NF-κB/KRT7/PD-L1 signaling axis that drives immune suppression and therapy resistance in CCA, highlighting its potential as a multi-target strategy for combined immunotherapy and chemoradiotherapy.

SSD inhibits the malignant phenotype of BCa by targeting PI3K/AKT to trigger ferroptosis. Its synergistic effect with GEM from the dual mechanisms of ferroptosis sensitization and epithelial-mesenchymal transition inhibition, providing an innovative combination strategy based on natural product active ingredients to overcome bladder cancer chemoresistance.

P1, N=31, Completed, K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc | Phase classification: P1/2 --> P1