ABCG2 protein expression in tumors of patients with non-resectable pancreatic cancer treated with gemcitabine and nab-paclitaxel
BackgroundATP-binding cassette (ABC) proteins are transmembrane efflux pumps that play a role in Multi Drug Resistance. ABCG2 and ABCB1 have been suggested as important mediators of resistance to chemotherapy (CTx) in pancreatic cancer (PC). We determined the expression of ABCG2 and ABCB1 proteins i...
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Frontiers Media S.A.
2025-06-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2025.1558184/full |
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| author | Susy Shim Susy Shim Mette Bak Nielsen Mikkel Eld Jan Stenvang Jan Stenvang Rasmus Froberg Brøndum Rasmus Froberg Brøndum Britta Weber Anne Krejbjerg Motavaf Morten Ladekarl Morten Ladekarl |
| author_facet | Susy Shim Susy Shim Mette Bak Nielsen Mikkel Eld Jan Stenvang Jan Stenvang Rasmus Froberg Brøndum Rasmus Froberg Brøndum Britta Weber Anne Krejbjerg Motavaf Morten Ladekarl Morten Ladekarl |
| author_sort | Susy Shim |
| collection | DOAJ |
| description | BackgroundATP-binding cassette (ABC) proteins are transmembrane efflux pumps that play a role in Multi Drug Resistance. ABCG2 and ABCB1 have been suggested as important mediators of resistance to chemotherapy (CTx) in pancreatic cancer (PC). We determined the expression of ABCG2 and ABCB1 proteins in PC and the impact of ABCG2 on outcome of treatment with gemcitabine and nab-paclitaxel (GemNab).Materials and methods140 patients with sufficient tissue for assessment that had initiated palliative treatment with GemNab for non-resectable PC from 2011 to 2019 were included at two institutions. From achieved tissue, new sections were cut and stained for ABCG2 and ABCB1. Staining was evaluated by consensus of maximum score by two pathologists. Progression-free survival (PFS) was the primary endpoint.ResultsABCB1 expression was observed in only one case (0.7%). ABCG2 was expressed in 33% but more frequently (50%) in specimens taken after gemcitabine-based (neo)adjuvant CTx (P=0.02). In multivariate analysis, ABCG2 expression was associated with an improved PFS (HR=0.64; 95%CI 0.43-0.94 (P=0.02)) of treatment with GemNab. Prior CTx, both in the (neo)adjuvant and palliative setting, was associated with shorter PFS of GemNab (P=0.03), and ABCG2 expression tended to correlate with improved PFS in these (P=0.07), but not in CTx-naïve patients (P=0.20). Similarly, a high ABCG2 expression was associated with improved overall survival (OS) only in patients with prior exposure to CTx (P=0.03). No associations of ABCG2 expression with CTx dosing or response rates were found.ConclusionWe found indications of upregulation of ABCG2 expression in tumors of patients previously exposed to gemcitabine, and ABCG2 expression correlated with efficacy of GemNab as assessed by PFS and OS in patients previously exposed to CTx, but not in those naïve to CTx. These findings diverge from the prevailing assumption that ABCG2 confers chemoresistance and suggest that in certain contexts, ABCG2 expression may reflect tumor adaptation or selection. Given the unexpected direction of this association, our findings should be interpreted as hypothesis-generating, and further studies are needed to elucidate underlying biological mechanisms and validate ABCG2 as a potential predictive biomarker in this setting. |
| format | Article |
| id | doaj-art-986bde2a512640df84e7929a1c3439e1 |
| institution | Kabale University |
| issn | 2234-943X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Oncology |
| spelling | doaj-art-986bde2a512640df84e7929a1c3439e12025-08-20T03:24:38ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-06-011510.3389/fonc.2025.15581841558184ABCG2 protein expression in tumors of patients with non-resectable pancreatic cancer treated with gemcitabine and nab-paclitaxelSusy Shim0Susy Shim1Mette Bak Nielsen2Mikkel Eld3Jan Stenvang4Jan Stenvang5Rasmus Froberg Brøndum6Rasmus Froberg Brøndum7Britta Weber8Anne Krejbjerg Motavaf9Morten Ladekarl10Morten Ladekarl11Department of Oncology and Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, DenmarkDepartment of Clinical Medicine, Aalborg University, Aalborg, DenmarkDepartment of Pathology, Aarhus University Hospital, Aarhus, DenmarkDepartment of Pathology, Aalborg University Hospital, Aalborg, DenmarkDepartment of Drug Design and Pharmacology, Copenhagen University, Copenhagen, DenmarkScandion Oncology A/S, Copenhagen, DenmarkDepartment of Clinical Medicine, Aalborg University, Aalborg, DenmarkCenter for Clinical Data Science, Aalborg University and Aalborg University Hospital, Aalborg, DenmarkDepartment of Oncology, Aarhus University Hospital, Aarhus, DenmarkDepartment of Oncology and Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, DenmarkDepartment of Oncology and Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, DenmarkDepartment of Clinical Medicine, Aalborg University, Aalborg, DenmarkBackgroundATP-binding cassette (ABC) proteins are transmembrane efflux pumps that play a role in Multi Drug Resistance. ABCG2 and ABCB1 have been suggested as important mediators of resistance to chemotherapy (CTx) in pancreatic cancer (PC). We determined the expression of ABCG2 and ABCB1 proteins in PC and the impact of ABCG2 on outcome of treatment with gemcitabine and nab-paclitaxel (GemNab).Materials and methods140 patients with sufficient tissue for assessment that had initiated palliative treatment with GemNab for non-resectable PC from 2011 to 2019 were included at two institutions. From achieved tissue, new sections were cut and stained for ABCG2 and ABCB1. Staining was evaluated by consensus of maximum score by two pathologists. Progression-free survival (PFS) was the primary endpoint.ResultsABCB1 expression was observed in only one case (0.7%). ABCG2 was expressed in 33% but more frequently (50%) in specimens taken after gemcitabine-based (neo)adjuvant CTx (P=0.02). In multivariate analysis, ABCG2 expression was associated with an improved PFS (HR=0.64; 95%CI 0.43-0.94 (P=0.02)) of treatment with GemNab. Prior CTx, both in the (neo)adjuvant and palliative setting, was associated with shorter PFS of GemNab (P=0.03), and ABCG2 expression tended to correlate with improved PFS in these (P=0.07), but not in CTx-naïve patients (P=0.20). Similarly, a high ABCG2 expression was associated with improved overall survival (OS) only in patients with prior exposure to CTx (P=0.03). No associations of ABCG2 expression with CTx dosing or response rates were found.ConclusionWe found indications of upregulation of ABCG2 expression in tumors of patients previously exposed to gemcitabine, and ABCG2 expression correlated with efficacy of GemNab as assessed by PFS and OS in patients previously exposed to CTx, but not in those naïve to CTx. These findings diverge from the prevailing assumption that ABCG2 confers chemoresistance and suggest that in certain contexts, ABCG2 expression may reflect tumor adaptation or selection. Given the unexpected direction of this association, our findings should be interpreted as hypothesis-generating, and further studies are needed to elucidate underlying biological mechanisms and validate ABCG2 as a potential predictive biomarker in this setting.https://www.frontiersin.org/articles/10.3389/fonc.2025.1558184/fullgemcitabinenab-paclitaxelATP-binding cassette proteinABCG2BRCPchemotherapy resistance |
| spellingShingle | Susy Shim Susy Shim Mette Bak Nielsen Mikkel Eld Jan Stenvang Jan Stenvang Rasmus Froberg Brøndum Rasmus Froberg Brøndum Britta Weber Anne Krejbjerg Motavaf Morten Ladekarl Morten Ladekarl ABCG2 protein expression in tumors of patients with non-resectable pancreatic cancer treated with gemcitabine and nab-paclitaxel Frontiers in Oncology gemcitabine nab-paclitaxel ATP-binding cassette protein ABCG2 BRCP chemotherapy resistance |
| title | ABCG2 protein expression in tumors of patients with non-resectable pancreatic cancer treated with gemcitabine and nab-paclitaxel |
| title_full | ABCG2 protein expression in tumors of patients with non-resectable pancreatic cancer treated with gemcitabine and nab-paclitaxel |
| title_fullStr | ABCG2 protein expression in tumors of patients with non-resectable pancreatic cancer treated with gemcitabine and nab-paclitaxel |
| title_full_unstemmed | ABCG2 protein expression in tumors of patients with non-resectable pancreatic cancer treated with gemcitabine and nab-paclitaxel |
| title_short | ABCG2 protein expression in tumors of patients with non-resectable pancreatic cancer treated with gemcitabine and nab-paclitaxel |
| title_sort | abcg2 protein expression in tumors of patients with non resectable pancreatic cancer treated with gemcitabine and nab paclitaxel |
| topic | gemcitabine nab-paclitaxel ATP-binding cassette protein ABCG2 BRCP chemotherapy resistance |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2025.1558184/full |
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