Pancreatic Ductal Adenocarcinoma

P=N/A, N=20, Not yet recruiting, M.D. Anderson Cancer Center

P=N/A, N=9, Active, not recruiting, GERCOR - Multidisciplinary Oncology Cooperative Group | Recruiting --> Active, not recruiting | N=72 --> 9

Future directions include multicenter prospective trials to validate multimodal models, standardize detection methods, and increase interdisciplinary collaboration. By integrating genomic, epigenetic, metabolic, and microbiome data, these models can better capture the complexity of PDAC, thereby improving patient outcomes through precision immunotherapy.

Due to its rarity, PACC remains a diagnostic challenge. It has a better prognosis than PDAC; radical resection is recommended.

Our study highlights the complementary diagnostic value of p53 and Smad4 IHC relative to molecular testing in PDAC, especially when tissue is limited, as commonly encountered in FNB specimens. The newly established Smad4 IHC classification system, which integrates an intermediate expression category into the conventional two-tier framework, demonstrates superior clinical utility and enhances predictive accuracy for SMAD4 genomic alterations.

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.

Our findings highlight a strong association between the upregulation of PDAC recurrence genes and the activation of metabolic pathways linked to obesity, diabetes, and inflammation. The consistent expression patterns across species suggest potential for developing targeted therapies to inhibit these metabolic pathways post-pancreatic cancer resection, potentially reducing fatality.

The efficacy of the CD40 agonist was partially dependent on CD8⁺ T cells. Our findings underscore the complex role of IL-1 signaling in modulating immune responses in PDAC and caution against pursuing IL-1R1 blockade, either as monotherapy or combined with agonistic CD40 antibodies, in clinical trials for PDAC.

In both immunocompetent and immunodeficient syngeneic PDAC models, we demonstrated that the combination of CAR-T cells with the intratumoural administration of oHSV30 significantly reduced tumour burden and prolonged the survival of tumour-bearing mice. Overall, our data suggest that oHSV30 can be a promising adjuvant for CAR-T therapy in PDAC.

In this review, we highlight these recent advances and discuss how lipid-driven circuits intersect with major oncogenic pathways, including KRAS effectors and phosphoinositide 3-kinase-AKT. By integrating mechanistic insights with therapeutic perspectives, we outline new opportunities to exploit lipid-based vulnerabilities in pancreatic cancer.

P=N/A, N=20, Recruiting, University of Massachusetts, Worcester | Not yet recruiting --> Recruiting

Through in situ analyses of T cell receptor (TCR) signaling, we found that ExTreg cells had the highest antigen-driven activation among tumor-infiltrating T cells. Reprogramming of intratumoral Treg cells into Th1-like effectors reveals plasticity and an anti-tumor capacity of these cells.