gemcitabine

Muscle-invasive bladder cancer(MIBC)carries a high risk of recurrence.The standard treatment has been cisplatin-based neoadjuvant chemotherapy(NAC)followed by radical cystectomy(RC), but nearly half of patients are cisplatin-ineligible and unable to receive optimal NAC.Furthermore, recurrence after NAC plus RC remains common, highlighting the need for effective adjuvant strategies.Recent advances in immune checkpoint inhibitors(ICIs)have revolutionized perioperative treatment paradigms.The phase Ⅲ CheckMate 274 trial demonstrated that adjuvant nivolumab significantly prolonged disease-free survival(DFS), particularly in PD-L1-positive patients.In the IMvigor010 trial, adjuvant atezolizumab did not improve DFS in the overall population, but a biomarker-driven subanalysis revealed marked benefit in patients with postoperative circulating tumor DNA(ctDNA)positivity.Based on these findings, the ongoing IMvigor011 trial restricts adjuvant atezolizumab to ctDNA-positive patients.The NIAGARA trial evaluated a comprehensive perioperative approach using neoadjuvant gemcitabine-cisplatin plus durvalumab followed by adjuvant durvalumab for 1 year.This regimen significantly improved DFS, overall survival(OS), and pathological complete response(pCR)rates without increasing Grade ≥3 toxicities.ctDNA has emerged as a promising biomarker for risk stratification and treatment monitoring, potentially enabling precision perioperative immunotherapy.This review summarizes pivotal phase Ⅲ trials of perioperative ICI therapy in MIBC and discusses the role of ctDNA-guided strategies, envisioning a shift from universal ICI administration to biomarker-driven, individualized perioperative approaches.

Accordingly, gemcitabine-cisplatin with nivolumab and platinum-based chemotherapy followed by maintenance avelumab remain validated evidence-based alternatives, particularly for cisplatin-eligible patients or in regions where enfortumab vedotin plus pembrolizumab is not readily accessible...Enfortumab vedotin monotherapy retains activity post-platinum and immune checkpoint inhibition, erdafitinib provides a targeted benefit in fibroblast growth factor receptor 3-altered tumors, and trastuzumab deruxtecan has emerged as a later-line option for HER2-positive disease. In parallel, circulating tumor DNA is an emerging biomarker with potential to individualize sequencing strategies, although its clinical application remains investigational. This review synthesizes current evidence and highlights practical considerations, emphasizing the need to balance therapeutic innovation with cost effectiveness, equitable access, and global applicability, while identifying critical research priorities in the post-enfortumab vedotin plus pembrolizumab era.

The patient underwent chemoradiotherapy consisting of 60 Gy in 30 fractions combined with gemcitabine+nab-paclitaxel...Histopathological evaluation revealed no viable cancer cells, showing only post-treatment changes, consistent with a pathological complete response(Grade 4). The postoperative course was uneventful, and at 6 months post-adrenalectomy, the patient remains recurrence-free without further adjuvant therapy.

In this phase 2 study (NCT05047991), patients with unresectable metastatic pancreatic adenocarcinoma were randomized to receive NALIRIFOX (liposomal irinotecan, 5-FU, leucovorin, and oxaliplatin) or gemcitabine plus nab-paclitaxel...≥ Grade 3 treatment-emergent adverse events (TEAEs) occurred in 73.1% of patients receiving NALIRIFOX and 84.6% of patients receiving gemcitabine plus nab-paclitaxel, respectively. Despite the premature termination (predetermined sample size of n = 153 not reached) of the study, NALIRIFOX demonstrated improvement in PFS compared with gemcitabine plus nab-paclitaxel, with a manageable safety profile in Chinese patients with advanced pancreatic adenocarcinoma.

circ72309 affected multiple steps in the gemcitabine metabolic pathway and its overexpression resulted in markedly increased gemcitabine sensitivity. Therefore, circ72309 expression in the pre‑treatment serum samples may serve as a predictor of gemcitabine sensitivity in patients with PC..

Furthermore, inhibition of PAK4 kinase activity promotes GEM-induced suppression of pancreatic cancer growth both in vitro and in vivo. Our study suggests that targeting PAK4 to promote GEM-induced pyroptosis may provide a new therapeutic approach for the treatment of pancreatic cancer.

In a thioacetamide-induced orthotopic ICC rat model, TAE combined with systemic GC reduces intratumoral Treg infiltration and VEGF expression. These findings indicate the combination therapy exerts superior immunomodulatory effects compared with TAE or GC monotherapy in rats.

P2, N=41, Active, not recruiting, Sun Yat-sen University | Recruiting --> Active, not recruiting | Trial primary completion date: Dec 2025 --> Jun 2025

P3, N=85, Not yet recruiting, Relmada Therapeutics, Inc.

The SKP2-CDK6 axis may drive PDAC progression and chemoresistance. Co-targeting SKP2 and CDK6 in combination with gemcitabine may represent a promising therapeutic approach, warranting further preclinical and clinical evaluation to improve outcomes for patients with PDAC.

This case suggests that an integrated approach, combining aggressive local therapy with systemic immunotherapy informed by biomarkers, can achieve a favorable outcome in selected patients with ICC. The identification of a high tumor mutational burden was crucial in guiding treatment and supports its potential as a predictive biomarker. This precision oncology strategy may improve the poor prognosis associated with this condition.

We experienced a case of pCR induced by GCS chemotherapy and pembrolizumab monotherapy. Although the direct contribution of pembrolizumab remains unclear, a possible synergistic effect with GCS chemotherapy was suggested, particularly in MSI-H tumors.