Document Type
Article
Publication Date
7-18-2024
Publication Title
Biomedicines
Abstract
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.
PubMed ID
39062169
Volume
12
Issue
7
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
Ferdous, Khandoker Usran; Tesfay, Mulu Z.; Cios, Aleksandra; Shelton, Randal S.; Hartupee, Conner; Urbaniak, Alicja; Chamcheu, Jean Christopher; Mavros, Michail N.; Giorgakis, Emmanouil; Mustafa, Bahaa; Simoes, Camila C.; Miousse, Isabelle R.; Basnakian, Alexei G.; Moaven, Omeed; Post, Steven R.; Cannon, Martin J.; Kelly, Thomas; and Nagalo, Bolni Marius, "Enhancing Neoadjuvant Virotherapy's Effectiveness by Targeting Stroma to Improve Resectability in Pancreatic Cancer" (2024). School of Medicine Faculty Publications. 2932.
https://digitalscholar.lsuhsc.edu/som_facpubs/2932
10.3390/biomedicines12071596
Included in
Neoplasms Commons, Therapeutics Commons, Virus Diseases Commons