Biomarker Profiling Revealed Carcinoembryonic Antigen as a Target of Artesunate in a Ductal Breast Cancer Patient

Publication type:
Journal article
Metadata:
Autoren
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000829941200023&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.21873/anticanres.15835
eISSN
1791-7530
Externe Identifier
  • Clarivate Analytics Document Solution ID: 3E4GA
  • PubMed Identifier: 35790273
ISSN
0250-7005
Ausgabe der Veröffentlichung
7
Zeitschrift
ANTICANCER RESEARCH
Schlüsselwörter
  • Cancer
  • chemotherapy
  • drug repurposing
  • individualized therapy
  • natural products
  • sesquiterpenoids
Paginierung
3483 - 3494
Datum der Veröffentlichung
2022
Status
Published
Titel
Biomarker Profiling Revealed Carcinoembryonic Antigen as a Target of Artesunate in a Ductal Breast Cancer Patient
Sub types
  • Article
Ausgabe der Zeitschrift
42

Data source: Web of Science (Lite)

Other metadata sources:
Autoren
DOI
10.21873/anticanres.15835
eISSN
1791-7530
ISSN
0250-7005
Ausgabe der Veröffentlichung
7
Zeitschrift
Anticancer Research
Sprache
en
Online publication date
2022
Paginierung
3483 - 3494
Datum der Veröffentlichung
2022
Status
Published
Herausgeber
Anticancer Research USA Inc.
Herausgeber URL
http://dx.doi.org/10.21873/anticanres.15835
Datum der Datenerfassung
2022
Titel
Biomarker Profiling Revealed Carcinoembryonic Antigen as a Target of Artesunate in a Ductal Breast Cancer Patient
Ausgabe der Zeitschrift
42

Data source: Crossref

Abstract
<h4>Background/aim</h4>Patients with metastatic tumors commonly have a poor prognosis. Frequently, patients suffering from progressive tumors have a high willingness for the compassionate use of non-approved medications. One of these medications is the antimalarial drug artesunate (ART) which also showed profound anticancer activity in vitro, in vivo, and in preliminary clinical pilot studies. Herein, we report on the compassionate use of ART in a patient with metastatic breast cancer.<h4>Patients and methods</h4>The clinical course of a Caucasian female who was diagnosed with ductal breast cancer at the age of 33 is described. Tumor markers in the blood have been measured, and tumor-associated protein expression has been determined by immunohistochemistry. Microscale thermophoresis and molecular docking in silico were used to study protein-drug interactions.<h4>Results</h4>The tumor responded to ART administered at doses of 150-300 mg daily, and the patient experienced a stabilization of her disease for 1.5 years. ART treatment caused no or minimal side-effects (headache, dizziness, slight tachycardia, slight stomach upset, slight fatigue). Tumor marker determination in the blood of the patient revealed a reduction of carcinoembryonic antigen (CEA), but not CA 27.29 or CA 15.3 levels. We hypothesized that the reduction of CEA levels might be due to binding of ART to this protein. Microscale thermophoresis with recombinant CEA indeed showed binding of ART to this protein in vitro. This result was verified by molecular docking in silico. Immunohistochemical biomarker profiling and computerbased quantification of biomarker expression in a tumor biopsy revealed strong expression of COX2, GRP78, CD71, GSTP1, and c-MYC but weak or minimal expression of VEGFR, P-glycoprotein, survivin, and LOX1.<h4>Conclusion</h4>Among a panel of tumor-related proteins tested, the interaction with CEA may have contributed to the anticancer activity of ART in this patient. It deserves further investigation whether CEA represents not only a valuable biomarker but also a treatment target. ART might be useful for the individualized treatment of metastatic breast tumors.
Addresses
  • Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Mainz, Germany.
Autoren
DOI
10.21873/anticanres.15835
eISSN
1791-7530
Externe Identifier
  • PubMed Identifier: 35790273
Open access
false
ISSN
0250-7005
Ausgabe der Veröffentlichung
7
Zeitschrift
Anticancer research
Schlüsselwörter
  • Humans
  • Carcinoma, Ductal, Breast
  • Breast Neoplasms
  • Carcinoembryonic Antigen
  • Female
  • Molecular Docking Simulation
  • Biomarkers, Tumor
  • Artesunate
Sprache
eng
Medium
Print
Paginierung
3483 - 3494
Datum der Veröffentlichung
2022
Status
Published
Datum der Datenerfassung
2022
Titel
Biomarker Profiling Revealed Carcinoembryonic Antigen as a Target of Artesunate in a Ductal Breast Cancer Patient.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
42

Data source: Europe PubMed Central

Abstract
BACKGROUND/AIM: Patients with metastatic tumors commonly have a poor prognosis. Frequently, patients suffering from progressive tumors have a high willingness for the compassionate use of non-approved medications. One of these medications is the antimalarial drug artesunate (ART) which also showed profound anticancer activity in vitro, in vivo, and in preliminary clinical pilot studies. Herein, we report on the compassionate use of ART in a patient with metastatic breast cancer. PATIENTS AND METHODS: The clinical course of a Caucasian female who was diagnosed with ductal breast cancer at the age of 33 is described. Tumor markers in the blood have been measured, and tumor-associated protein expression has been determined by immunohistochemistry. Microscale thermophoresis and molecular docking in silico were used to study protein-drug interactions. RESULTS: The tumor responded to ART administered at doses of 150-300 mg daily, and the patient experienced a stabilization of her disease for 1.5 years. ART treatment caused no or minimal side-effects (headache, dizziness, slight tachycardia, slight stomach upset, slight fatigue). Tumor marker determination in the blood of the patient revealed a reduction of carcinoembryonic antigen (CEA), but not CA 27.29 or CA 15.3 levels. We hypothesized that the reduction of CEA levels might be due to binding of ART to this protein. Microscale thermophoresis with recombinant CEA indeed showed binding of ART to this protein in vitro. This result was verified by molecular docking in silico. Immunohistochemical biomarker profiling and computerbased quantification of biomarker expression in a tumor biopsy revealed strong expression of COX2, GRP78, CD71, GSTP1, and c-MYC but weak or minimal expression of VEGFR, P-glycoprotein, survivin, and LOX1. CONCLUSION: Among a panel of tumor-related proteins tested, the interaction with CEA may have contributed to the anticancer activity of ART in this patient. It deserves further investigation whether CEA represents not only a valuable biomarker but also a treatment target. ART might be useful for the individualized treatment of metastatic breast tumors.
Date of acceptance
2022
Autoren
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/35790273
DOI
10.21873/anticanres.15835
eISSN
1791-7530
Ausgabe der Veröffentlichung
7
Zeitschrift
Anticancer Res
Schlüsselwörter
  • Cancer
  • chemotherapy
  • drug repurposing
  • individualized therapy
  • natural products
  • sesquiterpenoids
  • Artesunate
  • Biomarkers, Tumor
  • Breast Neoplasms
  • Carcinoembryonic Antigen
  • Carcinoma, Ductal, Breast
  • Female
  • Humans
  • Molecular Docking Simulation
Sprache
eng
Country
Greece
Paginierung
3483 - 3494
PII
42/7/3483
Datum der Veröffentlichung
2022
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2022
Titel
Biomarker Profiling Revealed Carcinoembryonic Antigen as a Target of Artesunate in a Ductal Breast Cancer Patient.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
42

Data source: PubMed

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