Pancreatic Ductal Adenocarcinoma

P1, N=300, Recruiting, M.D. Anderson Cancer Center | Active, not recruiting --> Recruiting | N=117 --> 300

P=N/A, N=700, Recruiting, Masaryk Memorial Cancer Institute | Trial primary completion date: Dec 2025 --> Jun 2026

Although PKM-ASO monotherapy had a limited effect in an immunodeficient mouse model of PDAC, synergy between PKM-ASO and anti-CTLA-4 immune checkpoint blockade (ICB), which targets Tregs, restricted tumor growth in an immunocompetent mouse model. Our findings provide preclinical support for combined antisense therapy and ICB for PDAC patients, highlighting the critical role of PKM2 in the TME and its potential as a therapeutic target.

Compact gene signatures stratified stage and survival and generalized to TCGA and ICGC cohorts. Functional assays confirmed greater invasiveness, altered redox balance, and mitochondrial dependence in advanced disease, suggesting stage-associated metabolic vulnerabilities.

By bridging nanotechnology, molecular imaging, and cancer biology, this review presents a comprehensive perspective on the next-generation MRI tools that could redefine early detection and treatment monitoring in pancreatic cancer. Addressing challenges of stroma penetration, biodistribution, and safety will be critical for their translation into clinical practice.

Gemcitabine-based chemotherapy regimens have shown limited antitumor effects for PDAC, and combination targets are urgently needed to restrict chemoresistance. Mechanistically, the focal adhesion kinase (FAK) inhibitor (IN10018) could restrict chemoresistance to Gem of PDAC by targeting SLC7A11-mediated ferroptosis through PI3K-Akt signaling pathway. For tumor microenvironment, IN10018 reduced the abundance of mesenchymal components and enhanced CD8+ T cell infiltration.

These findings support a model in which CS-A-bearing CSPGs on the surface of PDAC cells sequester Tmab and limit its productive engagement with HER2. Thus, enzymatic CS cleavage emerges as a glycan-editing strategy to potentiate Tmab activity in CS-A-rich tumors.

P=N/A, N=50, Recruiting, Massachusetts General Hospital | Not yet recruiting --> Recruiting

This phenotype is unique only to azole-containing benzodiazepines, including midazolam. Mechanistically, an unbiased phosphoproteomic approach revealed that ALP abrogates TLR4-mediated cytokine production in CAFs. These findings cumulatively support that ALP dampens CAF-mediated inflammatory signaling within the PDAC TME.

Multiplex immunofluorescence and semi-quantitative analysis confirmed increased prevalence of FABP4+ and VWF+ endothelial cells in areas with high MFAP5+ fibroblast expression, along with elevated VEGF and FGF signaling. Our study reveals a potential pro-tumorigenic mechanism of MFAP5+ fibroblasts in PDAC, suggesting that the MFAP5+ fibroblast-endothelial cell axis may represent a potential target for future therapeutic strategies.

Here, we use photoactivatable multi-inhibitor liposomes (PMILs) as a clinically translatable strategy to immunomodulate and enhance PDAC treatment using FDA-approved agents: minocycline for tumor priming by downregulating Tdp1, benzoporphyrin derivative incorporated into the liposomal bilayer for photodynamic priming (PDP) of the microenvironment, and irinotecan (IRI) for cytotoxicity. This combination achieved sustained local tumor regression, abscopal effects in untreated distant tumors, and a significant improvement in long-term survival (63%). By integrating clinically approved agents with non-overlapping mechanisms within a light-activated delivery platform, this approach enhances IRI efficacy, reprograms the TME, and promotes antitumor immunity, offering a translatable strategy to sensitize PDAC to chemo- and immunotherapy.

High cGDF-15 levels at baseline are a negative prognostic and predictive biomarker in localized, non-metastatic PDAC. Considering that GDF-15 is further up-regulated by neoadjuvant multiagent chemotherapy, our data, together with recent findings on clinical effects of GDF-15, provide a strong rationale for upfront therapeutic GDF-15 blockade in localized PDAC.