Enhancing Neoadjuvant Virotherapy's Effectiveness by Targeting Stroma to Improve Resectability in Pancreatic Cancer.

Autor: Ferdous KU; Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.; Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA., Tesfay MZ; Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.; Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA., Cios A; Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA., Shelton RS; College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA., Hartupee C; Division of Surgical Oncology, Department of Surgery, Louisiana State University (LSU) Health, New Orleans, LA 70112, USA., Urbaniak A; Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA., Chamcheu JC; Department of Biological Sciences and Chemistry, Southern University and A&M College, Baton Rouge, LA 70813, USA.; Division of Biotechnology and Molecular Medicine, Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA., Mavros MN; Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.; College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.; Department of Surgery, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA., Giorgakis E; Department of Surgery, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA., Mustafa B; Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA., Simoes CC; Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.; Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA., Miousse IR; Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA., Basnakian AG; Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.; Central Arkansas Veterans Healthcare System, John L. McClellan Memorial VA Hospital, Little Rock, AR 72205, USA., Moaven O; Division of Surgical Oncology, Department of Surgery, Louisiana State University (LSU) Health, New Orleans, LA 70112, USA.; Department of Interdisciplinary Oncology, Louisiana Cancer Research Center, Louisiana State University (LSU) Health, New Orleans, LA 70112, USA., Post SR; Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.; Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA., Cannon MJ; Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.; Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA., Kelly T; Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.; Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA., Nagalo BM; Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.; Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Jazyk: angličtina
Zdroj: Biomedicines [Biomedicines] 2024 Jul 18; Vol. 12 (7). Date of Electronic Publication: 2024 Jul 18.
DOI: 10.3390/biomedicines12071596
Abstrakt: About one-fourth of patients with pancreatic ductal adenocarcinoma (PDAC) are categorized as borderline resectable (BR) or locally advanced (LA). Chemotherapy and radiation therapy have not yielded the anticipated outcomes in curing patients with BR/LA PDAC. The surgical resection of these tumors presents challenges owing to the unpredictability of the resection margin, involvement of vasculature with the tumor, the likelihood of occult metastasis, a higher ratio of positive lymph nodes, and the relatively larger size of tumor nodules. Oncolytic virotherapy has shown promising activity in preclinical PDAC models. Unfortunately, the desmoplastic stroma within the PDAC tumor microenvironment establishes a barrier, hindering the infiltration of oncolytic viruses and various therapeutic drugs-such as antibodies, adoptive cell therapy agents, and chemotherapeutic agents-in reaching the tumor site. Recently, a growing emphasis has been placed on targeting major acellular components of tumor stroma, such as hyaluronic acid and collagen, to enhance drug penetration. Oncolytic viruses can be engineered to express proteolytic enzymes that cleave hyaluronic acid and collagen into smaller polypeptides, thereby softening the desmoplastic stroma, ultimately leading to increased viral distribution along with increased oncolysis and subsequent tumor size regression. This approach may offer new possibilities to improve the resectability of patients diagnosed with BR and LA PDAC.
Databáze: MEDLINE