Pancreatic Cancer

Treatment-induced EMT reduces GATA6+ populations and MHCI expression, which is restored by combining MEKi with HDAC inhibitors, enhancing GATA6+ tumor cells, MHCI, CD8+ T cell infiltration, tumor suppression, and survival. These findings suggest that therapeutic strategies promoting a GATA6-driven tumor cell state improve immune recognition of PDAC cells and potentiate anti-tumor cytotoxic effects.

P2, N=29, Active, not recruiting, Tianjin Medical University Cancer Institute and Hospital | Recruiting --> Active, not recruiting

P1/2, N=534, Recruiting, Revolution Medicines, Inc. | Phase classification: P1 --> P1/2 | N=210 --> 534 | Trial completion date: Nov 2026 --> Jun 2029 | Trial primary completion date: Nov 2026 --> Dec 2028

P=N/A, N=60, Not yet recruiting, University of Miami | Initiation date: Dec 2025 --> Apr 2026

P3, N=358, Active, not recruiting, Alliance for Clinical Trials in Oncology | Trial primary completion date: Jan 2027 --> Dec 2028

In this phase I study, we test a pooled synthetic long peptide vaccine targeting the six KRAS mutations (G12V, G12A, G12R, G12C, G12D, G13D) with ipilimumab and nivolumab in resected pancreatic adenocarcinoma. The vaccine also generates cross-reactive T cells that recognize more than one mutant KRAS antigen. These findings support the safety and diverse anti-tumor immunity of mutant KRAS vaccines (NCT04117087).

Trogocytosis-related CLDN18.2 inhibited the glucose uptake, glycolysis and cytotoxicity of tumour-infiltrating CD8+ T cells by promoting the ubiquitin-proteasomal degradation of β-catenin in PDAC. Therefore, targeting trogocytosis-related CLDN18.2+CD8+ T cells may be a promising therapeutic strategy to inhibit PDAC progression.

PDIA6, driven by KRASG12D, alleviates ICD and promotes immune evasion, functioning as a predictive biomarker to screen ICB-sensitive patients and a therapeutic target to improve ICB efficacy in PDAC with KRAS mutations.

As well as the cutting-edge field of chimeric cytokine engineering, including VHH-fusions, to selectively activate anti-tumor immunity, highlighting promising candidates in late-stage clinical trials. The successful application of these engineered cytokine strategies is crucial to unlocking effective immunotherapy for PDAC patients.

Therapy using miRNA mimics and inhibitors aims to restore gene expression balance, but delivery and stability concerns persist. Advances in nanotechnology are enabling increasingly targeted and effective miRNA-based therapies, potentially transforming the clinical management of pancreatic cancer (PC).

For experimental validation, umbelliprenin (UMB) was extracted from Ferula persica by preparative thin layer chromatography, and then, KYSE-30 cells were treated with UMB, alone and in combination with paclitaxel (PTX) for 48 h...The present findings highlight the potential of natural coumarins, particularly UMB, to inhibit the reductase activity of AKR1C3, thereby enhancing the efficacy of chemotherapy and radiotherapy. This positions UMB as a promising candidate for overcoming chemoradioresistance in GI carcinomas and paves the way for the development of innovative therapeutic strategies.