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Peer-reviewedCC BY 4.0Frontiers in Bioengineering and Biotechnology

Metabolic sensing in 3D models of pancreatic ductal adenocarcinoma: probing pH, oxygen, and lactate dynamics to decode chemoresistance

  • Anna Chiara Siciliano1,2
  • Stefania Forciniti1,2
  • Helena Iuele1,2
  • Federica Carnevali1,2
  • Giuseppe Gigli1,2,3
  • Loretta L. del Mercato1,2
  1. 1Institute of Nanotechnology, National Research Council (CNR-NANOTEC), Lecce, Italy
  2. 2Tecnomed Puglia – Technopole for Precision Medicine (Biotech Lecce Hub), Lecce, Italy
  3. 3Department of Experimental Medicine, University of Salento, Lecce, Italy
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Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies due to its late diagnosis, extensive desmoplasia, and strong chemoresistance. Recent advances in three-dimensional (3D) in vitro modelling have provided new insights into tumor-stroma interactions and metabolic adaptations that drive disease progression. This review summarizes the pathogenesis and tumor microenvironment (TME) hallmarks of PDAC, emphasizing the metabolic heterogeneity characterized by altered pH, oxygen, and lactate gradients. It discusses conventional and emerging therapeutic strategies, the molecular basis of drug resistance, and the role of the TME in treatment failure. Furthermore, it highlights the evolution of 3D experimental models as physiologically relevant tools to study PDAC biology and evaluate drug efficacy. Special attention is given to the integration of optical biosensors for non-invasive spatio-temporal monitoring of pH and metabolic fluctuations. These sensing technologies, coupled with advanced bioengineered models, are paving the way for precision oncology and patient-tailored strategies in pancreatic cancer.

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Cite

BibTeXRIS
BibTeX
@article{siciliano2026metabolic,
  title = {{Metabolic sensing in 3D models of pancreatic ductal adenocarcinoma: probing pH, oxygen, and lactate dynamics to decode chemoresistance}},
  author = {Anna Chiara Siciliano and Stefania Forciniti and Helena Iuele and Federica Carnevali and Giuseppe Gigli and Loretta L. del Mercato},
  journal = {Frontiers in Bioengineering and Biotechnology},
  year = {2026},
  month = oct,
  doi = {10.3389/fbioe.2026.1926254},
  url = {https://doi.org/10.3389/fbioe.2026.1926254},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Metabolic sensing in 3D models of pancreatic ductal adenocarcinoma: probing pH, oxygen, and lactate dynamics to decode chemoresistance
AU  - Anna Chiara Siciliano
AU  - Stefania Forciniti
AU  - Helena Iuele
AU  - Federica Carnevali
AU  - Giuseppe Gigli
AU  - Loretta L. del Mercato
PY  - 2026
DA  - 2026/10/12
JO  - Frontiers in Bioengineering and Biotechnology
DO  - 10.3389/fbioe.2026.1926254
UR  - https://doi.org/10.3389/fbioe.2026.1926254
AB  - Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies due to its late diagnosis, extensive desmoplasia, and strong chemoresistance. Recent advances in three-dimensional (3D) in vitro modelling have provided new insights into tumor-stroma interactions and metabolic adaptations that drive disease progression. This review summarizes the pathogenesis and tumor microenvironment (TME) hallmarks of PDAC, emphasizing the metabolic heterogeneity characterized by altered pH, oxygen, and lactate gradients. It discusses conventional and emerging therapeutic strategies, the molecular basis of drug resistance, and the role of the TME in treatment failure. Furthermore, it highlights the evolution of 3D experimental models as physiologically relevant tools to study PDAC biology and evaluate drug efficacy. Special attention is given to the integration of optical biosensors for non-invasive spatio-temporal monitoring of pH and metabolic fluctuations. These sensing technologies, coupled with advanced bioengineered models, are paving the way for precision oncology and patient-tailored strategies in pancreatic cancer.
SN  - 2296-4185
ER  -