gemcitabine

P2, N=82, Recruiting, National Cancer Center, Korea | Trial primary completion date: Dec 2025 --> Dec 2027

P1/2, N=71, Recruiting, Onconic Therapeutics Inc. | Phase classification: P1 --> P1/2 | N=30 --> 71 | Trial completion date: Jun 2026 --> Apr 2030 | Trial primary completion date: Mar 2026 --> Apr 2030

P2, N=55, Recruiting, Sun Yat-sen University | Not yet recruiting --> Recruiting

P3, N=514, Not yet recruiting, Sun Yat-sen University

P2, N=237, Active, not recruiting, Alliance for Clinical Trials in Oncology | Recruiting --> Active, not recruiting

Although pancreatic ductal adenocarcinoma (PDAC) is generally considered an immunologically "cold" tumor, approximately 20% of cases can be classified as immune-hot. Single-cell RNA sequencing revealed that the Gemcitabine-SAHA combination remodels the tumor microenvironment by enhancing CD8+ T cell function and depleting cancer-associated fibroblasts. Clinically, we defined a CD8high/FASNhigh/PARP9high signature that identifies an IE patient subgroup with poor survival, representing those most likely to benefit from the "Gemcitabine-Nivolumab-SAHA" triple-combination therapy.

Overcoming profoundly suppressed programmed cell death and an immunosuppressive tumor microenvironment (TME) remains a formidable challenge in gemcitabine-cisplatin-resistant muscle-invasive bladder cancer (GP-R MIBC). Consequently, when combined with an αPD-L1 antibody, this strategy effectively eradicated GP-R bladder tumors and suppressed recurrence in vivo, demonstrating compelling translational potential. In summary, our work presents a translatable nanotherapeutic strategy that resensitizes GP-R MIBC to chemo-immunotherapy by leveraging a synergistic "unlock-and-trigger" mechanism to reactivate pyroptosis.

Multiplex mediator profiling highlighted VEGF-A, GM-CSF, G-CSF, CCL2, CXCL1, IL-10, and TGF-β, and correlation analyses linked pro-angiogenic and granulocytic cues to vascular density, PMN-MDSC dominance, T cell imbalance, and tumor burden. These findings define, in an immune-intact 4 T1 model, a dose window in which GEM shifts from tumor suppression to tumor promotion in association with angiogenesis-related remodeling and functionally relevant myeloid immunosuppression, underscoring the need for biomarker-guided calibration of metronomic gemcitabine strategies and for validation in metastatic settings.

In KKU-213 A cells, PCE exhibited antagonistic and additive interactions with gemcitabine (Gem) and 5-fluorouracil (5-FU), respectively. In a nude mouse xenograft model, co-treatment with PCE and Gem significantly inhibited tumor growth and reduced Ki-67 expression compared to monotherapies. These findings suggest that PCE enhances the anticancer efficacy of Gem in CCA and may serve as a supportive combinatorial strategy.

The results from this multinational cohort suggest that high intratumoral infiltrations of TILs and MPs, along with low stromal FB densities, may be associated with better response to ICI-containing treatment in NPC. Further studies in larger, expanded cohorts are warranted, and prospective validation is needed.

We report the case of a woman with metastatic SMARCB1-deficient renal medullary carcinoma who developed acute hypoxic respiratory failure shortly after receiving combination gemcitabine and carboplatin. Discontinuation of gemcitabine and initiation of systemic steroids resulted in significant clinical improvement. This case highlights the diagnostic challenges of gemcitabine pulmonary toxicity in patients with metastatic lung disease and concurrent viral infection.

In addition, we combined PRMT5 inhibition with the DNA-damaging agents doxorubicin and gemcitabine, resulting in synergistic effects and increased cancer cell death in MTAP-deficient MPNST cell lines. Together, these findings identify PRMT5 as a compelling therapeutic target in MTAP-deficient MPNSTs. This PRMT5 inhibition strategy has strong translational potential for MPNSTs.