Pancreatic Adenocarcinoma

In each case, checkpoint blockade led to durable radiographic responses. We therefore propose that it is reasonable to assess combined positive score and tumor mutational burden in refractory or recurrent pancreatic cancers when initiation of ICB is being considered.

Although we have shown that the 3D environment dramatically sensitizes cells to MRTX1133 treatment, the synergistic effect of this drug combination is present in both 2D and 3D in the PANC1 pancreatic adenocarcinoma model, which showed high resistance to MRTX1133 in 2D. The effects of the combination treatment show an association with the inhibition of farnesylated regulatory proteins, including HRAS and RHEB, along with the expression level of KRAS. Our study warrants further investigation for the potential applicability of KRAS G12D inhibitors in combination with farnesyl-transferase inhibitors for the treatment of KRAS mutant pancreatic adenocarcinoma.

Mixed NET/non-NET tumors with distinct histology and molecular profiles might be better classified as collision tumors rather than MiNENs.

P2, N=14, Active, not recruiting, Spectrum Health Hospitals | Recruiting --> Active, not recruiting | Trial completion date: Dec 2026 --> Dec 2027 | Trial primary completion date: Dec 2026 --> Dec 2027

Our results suggest that TRPS1 IHC represents a highly accurate and reliable method for differentiating metastatic BC from PAC.

P2, N=10, Completed, Liverpool Hospital | Active, not recruiting --> Completed

Consequently, the tumor cells highly expressing NCF-1 obtained coincident accumulation of ROS and reduced glutathione (GSH) with expression of glutathione peroxidase 4 (GPX4), a quencher involved in ferroptosis. Unlike the conventional role of ROS as a representative cytotoxic factor, these findings suggest that NCF-1-mediated ROS generation may be required for expansive growth of PDAC and gastric cancers.

MICAL2 functions as a significant predictor and promising immunotherapeutic target for prognosis assessment in PAAD. It has a pivotal function in fostering the growth and migration of PAAD cells.

P1/2, N=46, Completed, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Recruiting --> Completed | N=30 --> 46 | Trial completion date: Dec 2024 --> Sep 2024 | Trial primary completion date: Dec 2024 --> Sep 2024

P=N/A, N=27, Not yet recruiting, University of Saskatchewan | Trial completion date: Mar 2026 --> Dec 2026 | Trial primary completion date: Mar 2026 --> Dec 2026

P2, N=76, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Dec 2025 --> Aug 2026 | Trial primary completion date: Dec 2024 --> Aug 2025

We reviewed cfDNA results from a local prospective solid tumour cohort (PREDiCT-l) and two randomized trials: CCTG CO.26 (durvalumab + tremelimumab [D+T] or best supportive care in metastatic colorectal cancer) and CCTG PA.7 (gemcitabine and nab-paclitaxel +/- D+T in metastatic pancreatic adenocarcinoma). CHIP is common in patients with solid tumours. Although not appearing to impact rates of adverse events, CHIP may impact outcomes from immunotherapy or chemotherapy.

P2, N=46, Recruiting, Wake Forest University Health Sciences | Suspended --> Recruiting

P2, N=194, Active, not recruiting, Trishula Therapeutics, Inc. | Recruiting --> Active, not recruiting

CD73 could be used to predict the prognosis of patients with several cancers. The potential functional mechanism of CD73 involved in cancer progress may not only dependent on its immunomodulatory effects.

P=N/A, N=110, Active, not recruiting, GERCOR - Multidisciplinary Oncology Cooperative Group | Unknown status --> Active, not recruiting | Trial completion date: Oct 2020 --> Jan 2025

P2, N=20, Active, not recruiting, Australasian Gastro-Intestinal Trials Group | Recruiting --> Active, not recruiting

The median OS of 58 patients in the FAT1 high-expression group and 134 patients in the FAT1 low-expression group were 18.89 and 25.84 months, respectively, and the difference was not statistically significant (χ²=1.93, P=0.165). FAT1 gene is highly expressed in pancreatic adenocarcinoma tissues, may play an oncogenic role in pancreatic adenocarcinoma, may be an adverse influence on overall survival and progression-free survival of patients; FAT1 gene may be involved in multiple immune-related pathways and promote tumor immune escape.

P1, N=39, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting

P=N/A, N=3500, Recruiting, Queen Mary University of London | Trial completion date: Feb 2025 --> Aug 2026 | Trial primary completion date: Feb 2025 --> Aug 2026

P1/2, N=104, Completed, University of Pennsylvania | Active, not recruiting --> Completed | Trial completion date: Jun 2026 --> Oct 2024

CA 19-9 non-expression is associated with distant metastatic disease at diagnosis and with death in resected non-metastatic patients compared to normal-range CA 19-9 levels. This clinically relevant subgroup requires alternative biomarkers, and may need consideration of more extensive preoperative staging and intensive perioperative systemic therapy.

CD8RGs play an important role in regulating the TME of PAAD. Five hub genes-BCL11A, KLK11, GNG7, PHOSPHO1, and VCAM1-are closely associated with the prognosis of PAAD patients, providing new references for the exploration of biomarkers. Furthermore, our findings offer novel insights for clinical decision-making.

CK19 as a prognostic marker in NETs has potential for further study. The results with our protocol for GPC3 immunohistochemistry suggest that pancreatic cancer may be a less promising target for GPC3-targeted immunotherapies than previously thought.

Thus, in pancreatic adenocarcinoma, the p53 protein level is a relevant marker for prognosis, and cancers having a high p53 protein amount show a shortened patients' survival. In contrast, for this cancer entity, the TP53 mutation status or the protein amount of prominent p53 target genes on their own seems not to have a significant impact on survival.

P1, N=13, Active, not recruiting, University of Pennsylvania | Recruiting --> Active, not recruiting

P3, N=609, Recruiting, Seoul National University Hospital | Not yet recruiting --> Recruiting

Combination chemotherapy regimens using fluorouracil (fluorouracil, oxaliplatin, leucovorin, and irinotecan; and fluorouracil, leucovorin, and oxaliplatin) or gemcitabine with albumin-bound paclitaxel have the potential to improve overall survival for patients with advanced disease. Alternative approaches to incorporate immunotherapy have shown more promise such as use of immune checkpoint inhibitors for selected patients in the maintenance setting and potential vaccine therapies in the postsurgery adjuvant setting. It is vital to perform molecular profiling in all patients with PDAC to identify potential treatment targets, and to enroll patients in clinical trials whenever possible.

Furthermore, we demonstrate the synergistic efficacy of combining STK39 inhibition with PARP inhibitors in suppressing and reversing PAAD growth. This study not only provides new insights into the molecular dynamics of H2A.X phosphorylation but also highlights the therapeutic potential of targeting STK39 to enhance PARPi sensitivity in PAAD (created with BioRender).

P=N/A, N=50, Not yet recruiting, Institut Bergonié

P=N/A, N=700, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Oct 2024 --> Oct 2025 | Trial primary completion date: Oct 2024 --> Oct 2025

This study provides a new perspective for understanding the characteristics of the hepatic TME in patients with liver metastatic cancer. And it provides a subset of macrophages specifically associated with the liver metastasis of pancreatic cancer, and its detection and intervention have potential value for preventing the metastasis of pancreatic cancer to the liver.

Moreover, we identified specific subsets of FAP+ and podoplanin+/cadherin-11+ CAFs enriched in patients with negative prognosis. The present study provides new general insights into the complexity of the PDAC microenvironment by defining phenotypic heterogeneities and spatial distributions of CAFs, thus suggesting different functions of their subtypes in the PDAC microenvironment.

P1, N=10, Completed, Karie D. Runcie, MD | Active, not recruiting --> Completed

P=N/A, N=134, Recruiting, Varian, a Siemens Healthineers Company | Trial completion date: Feb 2027 --> Feb 2028 | Trial primary completion date: Feb 2025 --> Feb 2026

Our results re-emphasize the importance of a robust Post Marketing Surveillance system and suggest this FAERS database based analysis provides an updated, independent information on Abraxane related AEs to enrich its safety profile. A process of continuous vigilance and additional investigations on specific areas that may have some undesired events are imperative to increase our knowledge on how Abraxane should be handled in terms of its safety.

P1/2, N=135, Recruiting, Phanes Therapeutics | Trial completion date: Apr 2026 --> Apr 2028 | Trial primary completion date: Dec 2025 --> Dec 2027

Our study demonstrated that circ_0124346 regulates lipid metabolism in PAAD cells via the miR-223-3p/ACSL3 axis, suggesting that targeting circ_0124346 may serve as a potential strategy for treating PAAD and assisting in its diagnosis.

P1, N=18, Not yet recruiting, Masonic Cancer Center, University of Minnesota

Additionally, low CLDN18.2 expression was linked to favorable prognosis. Our study reveals the potential value of CLDN18.2 for tumor prognosis and targeted therapy in various cancers, especially upper gastrointestinal tract cancers.

Further, the proportions of T cells and cluster of differentiation 8 (CD8) T cells, and the expression levels of immune checkpoints, such as cluster of differentiation 274 (CD274) and lymphocyte activating gene 3 (LAG3), differed significantly between the two risk groups. The eight identified KDE-ITGs in PAAD were used to establish a new prognosis model, which might have clinical application, especially in immunotherapy.

A CD8T cell-related signature demonstrated robust prognostic predictive performance for GC. Our findings may reveal novel insights into the diagnosis and treatment of GC.