ArticleCancer science2008
Overexpression of carboxylesterase-2 results in enhanced efficacy of topoisomerase I inhibitor, irinotecan (CPT-11), for multiple myeloma.
Article in Cancer science, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 38 citations in OpenAlex.
- A Phase I/II Study for Dose-finding, and to Investigate the Safety, Pharmacokinetics and Preliminary Efficacy of NK012, an SN-38-Incorporating Macromolecular Polymeric Micelle, in Patients with Multiple Myeloma.Internal medicine (Tokyo, Japan) · 2018Trial
- Prodrugs in Oncology: Bioactivation and Impact on Therapeutic Efficacy and Toxicity.International journal of molecular sciences · 2025Review
- Activity-Based Dicyanoisophorone Derivatives: Fluorogenic Toolbox Enables Direct Visualization and Monitoring of Esterase Activity in Tumor Models.Analytical chemistry · 2024Article
- Insights into the Degradation of Polymer-Drug Conjugates by an Overexpressed Enzyme in Cancer Cells.Journal of medicinal chemistry · 2023Article
- Heterogenous chemosensitivity of a panel of organoid lines derived from small cell neuroendocrine carcinoma of the uterine cervix.Human cell · 2021Article
- Prognostic significance of esterase gene expression in multiple myeloma.British journal of cancer · 2021Article
- Combined use of irinotecan and p53 activator enhances growth inhibition of mesothelioma cells.FEBS open bio · 2020Article
- Dual-Activatable Cell Tracker for Controlled and Prolonged Single-Cell Labeling.ACS chemical biology · 2020Article
- Human carboxylesterases: a comprehensive review.Acta pharmaceutica Sinica. B · 2018Review
- Article
- Enzyme/Prodrug Systems for Cancer Gene Therapy.Current pharmacology reports · 2016Article
- Human carboxylesterase 2: Studies on the role of glycosylation for enzymatic activity.Biochemistry and biophysics reports · 2016Article
- Carboxylesterase 2 as a Determinant of Response to Irinotecan and Neoadjuvant FOLFIRINOX Therapy in Pancreatic Ductal Adenocarcinoma.Journal of the National Cancer Institute · 2015Article
- Effect of Cellular Location of Human Carboxylesterase 2 on CPT-11 Hydrolysis and Anticancer Activity.PloS one · 2015Article
- Identification of Toyocamycin, an agent cytotoxic for multiple myeloma cells, as a potent inhibitor of ER stress-induced XBP1 mRNA splicing.Blood cancer journal · 2012Article
- Irinotecan pharmacogenomics.Pharmacogenomics · 2010Review
- Cancer therapies utilizing the camptothecins: a review of the in vivo literature.Molecular pharmaceutics · 2010Review
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Authors and funding
17 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multiple myeloma (MM) remains an incurable disease and further development of novel agents is needed. Because constitutive expression of topoisomerase I (TopoI) in MM cells and the efficacy of SN-38, an active metabolite of irinotecan (CPT-11), have been reported, we investigated the therapeutic potential of CPT-11. Of the eight MM cell lines analyzed, four showed 50% inhibitory concentration values of less than 2 microg/mL for CPT-11 and less than 2 ng/mL for SN-38. This efficacy was partly explained by the high expression level of human carboxylesterase-2 (hCE-2) in MM cells. Interestingly, high expression of hCE-2 represented the nature of normal plasma cells, suggesting that hCE-2 could efficiently generate SN-38 within the plasma cells. As expected, higher sensitivity to CPT-11 was observed in hCE-2-overexpressing U266 cells than mock U266 cells. On the other hand, the expression levels of hCE-1, TopoI, UGT1A and ABCG2 did not seem to be associated with the sensitivity of MM cells to CPT-11. In a murine xenograft model inoculated s.c. with RPMI8226 cells, administration of CPT-11 alone significantly reduced the tumor volume. When a combination of CPT-11 and bortezomib was administered, the subcutaneous tumors completely disappeared. Thus, clinical trials on CPT-11 in patients with relapsed or refractory MM are warranted.
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