Gemcitabine effects on tumor microenvironment of pancreatic ductal adenocarcinoma: Special focus on resistance mechanisms and metronomic therapies
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is considered one of the deadliest malignancies, with dismal survival rates and extremely prevalent chemoresistance. Gemcitabine is one of the primary treatments used in treating PDACs, but its benefits are limited due to chemoresistance, which could be attributed to interactions between the tumor microenvironment (TME) and intracellular processes. In preclinical models, certain schedules of administration of gemcitabine modulate the TME in a manner that does not promote resistance. Metronomic therapy constitutes a promising strategy to overcome some barriers associated with current PDAC treatments. This review will focus on gemcitabine's mechanism in treating PDAC, combination therapies, gemcitabine's interactions with the TME, and gemcitabine in metronomic therapies.
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The PDAC TME limits the delivery of GEM to tumours by downregulating concentrative and equilibrative nucleoside transporters and enzymes involved in GEM transport and metabolism.
“the PDAC TME limits the delivery of GEM to tumours by downregulating the concentrative and equilibrative nucleoside transporters and enzymes involved in GEM transport and metabolism, respectively [56]”
From Pyrvinium Pamoate Alone and With Gemcitabine Exhibits Anti‐Pancreatic Cancer Activity in <scp>2D</scp> and <scp>3D</scp> Cell Culture Models (2024) · cites this paper as [56]
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Serala, K., Bai, J., & Prince, S. (2024) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.70222 · Cited by 6 · see citing works
- Authors
- Natu, J., & Nagaraju, G. P.
- Affiliations
- University of Alabama (US)
- Corresponding author
- Nagaraju, Ganji Purnachandra
- Venue
- Cancer Letters
- Publisher
- Elsevier BV
- Published
- 2023-10
- Volume
- 573
- Pages
- 216382
- ISSN
- 0304-3835 (ISSN-L)
- OpenAlex
- W4386391959
- Cited by
- 73
- References
- 5
- Citations by year
- 2026: 17 · 2025: 27 · 2024: 27 · 2023: 2
- FWCI
- 2.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Cancer Letters (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Health Sciences › Medicine › Surgery › Pancreatitis Pathology and Treatment
- Health Sciences › Medicine › Surgery › Cholangiocarcinoma and Gallbladder Cancer Studies
- Keywords
- gemcitabine, pancreatic ductal adenocarcinoma, tumor microenvironment, chemoresistance, metronomic chemotherapy, drug resistance mechanisms, combination therapy
- MeSH terms
- Gemcitabine, Humans, Pancreatic Neoplasms, Carcinoma, Pancreatic Ductal, Tumor Microenvironment
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