ArticleClinical cancer research : an official journal of the American Association for Cancer Research2021
Altered Gemcitabine and Nab-paclitaxel Scheduling Improves Therapeutic Efficacy Compared with Standard Concurrent Treatment in Preclinical Models of Pancreatic Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 16 citations in OpenAlex.
- High SMAD4 Expression is Associated with Improved Clinical Outcomes in Patients with Resectable Pancreatic Cancer: An Analysis of NRG Oncology/RTOG 9704.International journal of radiation oncology, biology, physics · 2026Article
- Tumor microenvironment phenotyping guides precision therapy in unresectable pancreatic cancer.World journal of gastrointestinal oncology · 2025Review
- AZD5153 enhances the chemo-sensitivity of gemcitabine on pancreatic cancer cells in vitro and in vivo.Cancer cell international · 2025Article
- Phase I study of oral metronomic gemcitabine (D07001) in patients with advanced solid tumors.The oncologist · 2025Article
- Article
- RAS-RAF-miR-296-3p signaling axis increases Rad18 expression to augment radioresistance in pancreatic and thyroid cancers.Cancer letters · 2024Article
- Nutrient scavenging-fueled growth in pancreatic cancer depends on caveolae-mediated endocytosis under nutrient-deprived conditions.Science advances · 2024Article
- First-in-Class Humanized Antibody against Alternatively Spliced Tissue Factor Augments Anti-Metastatic Efficacy of Chemotherapy in a Preclinical Model of Pancreatic Ductal Adenocarcinoma.International journal of molecular sciences · 2024Article
- JNTX-101, a novel albumin-encapsulated gemcitabine prodrug, is efficacious and operates via caveolin-1-mediated endocytosis.Molecular therapy oncolytics · 2023Article
- Optimize the combination regimen of Trastuzumab and Nab-paclitaxel in HER2-positive tumors via modulating Caveolin-1 expression by lovastatin.Asian journal of pharmaceutical sciences · 2022Article
- Deregulation of AKT-mTOR Signaling Contributes to Chemoradiation Resistance in Lung Squamous Cell Carcinoma.Molecular cancer research : MCR · 2022Article
- Caveolae-Associated Molecules, Tumor Stroma, and Cancer Drug Resistance: Current Findings and Future Perspectives.Cancers · 2022Review
- circFARP1 enables cancer-associated fibroblasts to promote gemcitabine resistance in pancreatic cancer via the LIF/STAT3 axis.Molecular cancer · 2022Article
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
purposeConcurrent gemcitabine and nab-paclitaxel treatment is one of the preferred chemotherapy regimens for metastatic and locally advanced pancreatic ductal adenocarcinoma (PDAC). Previous studies demonstrate that caveolin-1 (Cav-1) expression is critical for nab-paclitaxel uptake into tumors and correlates with response. Gemcitabine increases nab-paclitaxel uptake by increasing Cav-1 expression. Thus, we hypothesized that pretreatment with gemcitabine would further enhance the sensitivity of PDAC to nab-paclitaxel by increasing Cav-1 expression and nab-paclitaxel uptake. EXPERIMENTAL
designWe investigated the sensitivity of different gemcitabine and nab-paclitaxel treatment regimens in a panel of PDAC cell lines and orthotopic xenograft models. The sensitivity of different treatment regimens was compared with the standard concurrent treatment.
resultsPretreatment with gemcitabine before nab-paclitaxel increased Cav-1 and albumin uptake and significantly decreased proliferation and clonogenicity compared with concurrent treatment, which correlated with increased levels of apoptosis. Cav-1 silencing reduced the uptake of albumin, and therapeutic advantage was observed when cells were pretreated with gemcitabine prior to nab-paclitaxel. In addition, we observed that pretreatment with gemcitabine resulted in partial synchronization of cells in the G
conclusionsPretreatment with gemcitabine significantly increased nab-paclitaxel uptake and correlated with an increased treatment efficacy and survival benefit in preclinical models, compared with standard concurrent treatment. These results justify preclinical and clinical testing of this altered scheduling combination.
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