Engineered bacteria-mediated stromal remodeling in pancreatic ductal adenocarcinoma: therapeutic opportunities and translational limits-a narrative review.
- 1The First Clinical Medical College of Gansu University of Chinese Medicine, Lanzhou, China.
- 2Department of Radiation Oncology II, Gansu Provincial Hospital, Lanzhou, China.
Abstract
Pancreatic ductal adenocarcinoma (PDAC) remains one of the gastrointestinal malignancies least amenable to durable therapeutic control. Resistance is generated by the intrinsic aggressiveness of the malignant epithelium and is reinforced by a compact desmoplastic microenvironment in which extracellular matrix (ECM) accumulation, vascular compression, impaired perfusion, and immune exclusion are closely interlocked. The limited clinical yield of nonselective stromal-depleting strategies has sharpened interest in localized, controllable, and context-sensitive stromal remodeling. This narrative review synthesizes the biological rationale, mechanistic routes, therapeutic implications, and translational limits of engineered bacteria-mediated stromal remodeling in PDAC. PubMed, Web of Science, and Scopus were searched from database inception to 30 April 2026 using Medical Subject Headings (MeSH) and free-text terms related to PDAC, engineered bacteria, bacterial cancer therapy, tumor stroma, ECM remodeling, hyaluronan, collagen, drug delivery, immune sensitization, and clinical translation. A targeted update of PubMed and a cross-registry search of ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) were performed on 24 July 2026. English-language full-text literature was prioritized, and PDAC-specific evidence was distinguished from broader bacteria-based oncology evidence. Engineered bacterial systems are appealing living therapeutic platforms because tumor tropism, preferential residence in hypoxic or necrotic tumor territories, and programmable local payload release can be assembled within a single biological chassis. In PDAC models, bacteria-mediated stromal remodeling has been investigated through hyaluronan degradation, collagen depletion, dual ECM co-depletion, and indirect modulation of pancreatic stellate cell (PSC)/cancer-associated fibroblast-associated fibrotic programs. These approaches may improve intratumoral drug penetration, mitigate pressure-related transport barriers, increase immune-cell access, and support multimodal local therapy. The evidential base, however, remains predominantly preclinical; direct clinical validation in PDAC is still limited. At present, engineered bacteria should be interpreted primarily as local stromal-opening and delivery-enabling platforms, not as clinically established therapies for PDAC. Their translational value will depend on whether stromal remodeling can be delivered safely, reproducibly, and in a manner that is measurable in patients.
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BibTeX
@article{wang2026engineered,
title = {{Engineered bacteria-mediated stromal remodeling in pancreatic ductal adenocarcinoma: therapeutic opportunities and translational limits-a narrative review.}},
author = {Tao Wang and Xinying Zhu and Xingyu Li and Zhoutai Chai and Xiaojun Liu},
journal = {Journal of gastrointestinal oncology},
year = {2026},
month = aug,
doi = {10.21037/jgo-2026-0612},
url = {https://europepmc.org/article/MED/42996866},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Engineered bacteria-mediated stromal remodeling in pancreatic ductal adenocarcinoma: therapeutic opportunities and translational limits-a narrative review.
AU - Tao Wang
AU - Xinying Zhu
AU - Xingyu Li
AU - Zhoutai Chai
AU - Xiaojun Liu
PY - 2026
DA - 2026/08/10
JO - Journal of gastrointestinal oncology
DO - 10.21037/jgo-2026-0612
UR - https://europepmc.org/article/MED/42996866
AB - Pancreatic ductal adenocarcinoma (PDAC) remains one of the gastrointestinal malignancies least amenable to durable therapeutic control. Resistance is generated by the intrinsic aggressiveness of the malignant epithelium and is reinforced by a compact desmoplastic microenvironment in which extracellular matrix (ECM) accumulation, vascular compression, impaired perfusion, and immune exclusion are closely interlocked. The limited clinical yield of nonselective stromal-depleting strategies has sharpened interest in localized, controllable, and context-sensitive stromal remodeling. This narrative review synthesizes the biological rationale, mechanistic routes, therapeutic implications, and translational limits of engineered bacteria-mediated stromal remodeling in PDAC. PubMed, Web of Science, and Scopus were searched from database inception to 30 April 2026 using Medical Subject Headings (MeSH) and free-text terms related to PDAC, engineered bacteria, bacterial cancer therapy, tumor stroma, ECM remodeling, hyaluronan, collagen, drug delivery, immune sensitization, and clinical translation. A targeted update of PubMed and a cross-registry search of ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) were performed on 24 July 2026. English-language full-text literature was prioritized, and PDAC-specific evidence was distinguished from broader bacteria-based oncology evidence. Engineered bacterial systems are appealing living therapeutic platforms because tumor tropism, preferential residence in hypoxic or necrotic tumor territories, and programmable local payload release can be assembled within a single biological chassis. In PDAC models, bacteria-mediated stromal remodeling has been investigated through hyaluronan degradation, collagen depletion, dual ECM co-depletion, and indirect modulation of pancreatic stellate cell (PSC)/cancer-associated fibroblast-associated fibrotic programs. These approaches may improve intratumoral drug penetration, mitigate pressure-related transport barriers, increase immune-cell access, and support multimodal local therapy. The evidential base, however, remains predominantly preclinical; direct clinical validation in PDAC is still limited. At present, engineered bacteria should be interpreted primarily as local stromal-opening and delivery-enabling platforms, not as clinically established therapies for PDAC. Their translational value will depend on whether stromal remodeling can be delivered safely, reproducibly, and in a manner that is measurable in patients.
SN - 2078-6891
SN - 2219-679X
ER -