Background: Pancreatic ductal adenocarcinoma (PDAC) presents a redoubtable challenge due to late-stage diagnosis and limited treatment options, necessitating innovative therapeutic strategies.
Methods: Here, we report our results investigating the safety and efficacy of talimogene laherparepvec (T-VEC), an FDA-approved oncolytic herpes simplex virus type 1, in patients with advanced PDAC. Nine patients with treatment-refractory advanced PDAC received escalating doses of T-VEC via endoscopic injection.
Results: While no objective responses were observed, stable disease was achieved in 44% of patients, with a median overall survival of 7.8 months, including one patient who survived 28 months. Adverse events were manageable, with the maximum tolerated dose determined to be 108 PFU/mL.
Conclusion: Our findings underscore the feasibility of intratumoral T-VEC administration in advanced PDAC. Further investigation, particularly in combination with immunotherapies administered systemically is warranted to more optimally assess T-VEC in this challenging malignancy.ClinicalTrials.gov Identifier: NCT03086642.
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http://dx.doi.org/10.1093/oncolo/oyae200 | DOI Listing |
Chembiochem
January 2025
Purdue University College of Engineering, Weldon School of Biomedical Engineering, 723 W. Michigan St., SL 220K, IN 46202, Indianapolis, UNITED STATES OF AMERICA.
Pancreatic ductal adenocarcinoma (PDAC) is marked by significant desmoplastic reactions, or the accumulation of excessive extracellular matrices. PDAC stroma has abnormally high stiffness, which alters cancer cell behaviors and creates a barrier for effective drug delivery. Unfortunately, clinical trials using a combination of chemotherapy and matrix-degrading enzyme have led to disappointing results, as the degradation of stromal tissue likely accelerated the dissemination of cancer cells.
View Article and Find Full Text PDFMol Oncol
January 2025
System Biology, Graduate School of Advanced Preventive Medical Sciences, Kanazawa University, Japan.
Pancreatic ductal adenocarcinoma (PDAC) is a disease with poor prognosis due to diagnostic and therapeutic limitations. We previously identified cystatin A (CSTA) as a PDAC biomarker and have conducted the present study to investigate the antitumor effects of CSTA. PDAC murine models were established with genetically modified PAN02 tumor cell lines to evaluate the antitumor immune response.
View Article and Find Full Text PDFNat Cancer
January 2025
Department of Molecular and Medical Genetics, Oregon Health and Science University, Portland, OR, USA.
Patients with metastatic pancreatic ductal adenocarcinoma survive longer if disease spreads to the lung but not the liver. Here we generated overlapping, multi-omic datasets to identify molecular and cellular features that distinguish patients whose disease develops liver metastasis (liver cohort) from those whose disease develops lung metastasis without liver metastases (lung cohort). Lung cohort patients survived longer than liver cohort patients, despite sharing the same tumor subtype.
View Article and Find Full Text PDFDiscov Oncol
January 2025
Hematology Oncology Associates of CNY, Syracuse, USA.
Pancreatic cancer is a highly aggressive malignancy with the majority of patients presenting at a late stage with unresectable or metastatic disease. Even with first line treatment, median survival is approximately 11 months in patients with advanced PDAC. This report details the unique case of a patient that presented with peritoneal metastases from an adenocarcinoma of the body of the pancreas, had a remarkable response to palliative chemotherapy and is alive without evidence of disease 12 months following cessation of all active treatment.
View Article and Find Full Text PDFTher Adv Med Oncol
January 2025
Centro Integral Oncológico Clara Campal HM CIOCC, Hospital Universitario HM Sanchinarro, Madrid, Spain.
Treatment with pegylated nanoliposomal irinotecan (nal-IRI) plus 5-fluorouracil/leucovorin (folinic acid; 5-FU/LV) has demonstrated remarkable efficacy for metastatic pancreatic ductal adenocarcinoma (PDAC) in clinical trials. However, real-world data on the effectiveness of nal-IRI+5-FU/LV is heterogeneous and is lacking in Spain. To assess the effectiveness and safety of nal-IRI+5-FU/LV in real-life PDAC patients in Spain.
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