Large set data mining reveals overexpressed GPCRs in prostate and breast cancer: potential for active targeting with engineered anti-cancer nanomedicines
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Authors
Albrecht, Hugo
Author (Corporation)
Publication date
05/2018
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Course of study
Collections
Type
01A - Journal article
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Editor (Corporation)
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Parent work
Oncotarget
Special issue
DOI of the original publication
Link
Series
Series number
Volume
9
Issue / Number
38
Pages / Duration
24882-24897
Patent number
Publisher / Publishing institution
Impact Journals LLC
Place of publication / Event location
Edition
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Abstract
Over 800 G-protein-coupled receptors (GPCRs) are encoded by the human genome and many are overexpressed in tumors. GPCRs are triggered by ligand molecules outside the cell and activate internal signal transduction pathways driving cellular responses. The receptor signals are desensitized by receptor internalization and this mechanism can be exploited for the specific delivery of ligand-linked drug molecules directly into cells. Detailed expression analysis in cancer tissue can inform the design of GPCR-ligand decorated drug carriers for active tumor cell targeting. The active targeting process utilizes ligand receptor interactions leading to binding and in most cases internalization of the ligand-attached drug carrier resulting in effective targeting of cancer cells. In this report public microarray data from the Gene Expression Omnibus (GEO) repository was used to identify overexpressed GPCRs in prostate and breast cancer tissues. The analyzed data confirmed previously known cancer receptor associations and identified novel candidates for potential active targeting. Prioritization of the identified targeting receptors is also presented based on high expression levels and frequencies in cancer samples but low expression in healthy tissue. Finally, some selected examples were used in ligand docking studies to assess the feasibility for chemical conjugation to drug nanocarriers without interference of receptor binding and activation. The presented data demonstrate a large untapped potential to improve efficacy and safety of current and future anti-cancer compounds through active targeting of GPCRs on cancer cells.
Keywords
GCPR, Pathology, cancer, meta-data, nanocarrier, targeted chemotherapy
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ISBN
ISSN
1949-2553
Language
English
Created during FHNW affiliation
Yes
Strategic action fields FHNW
Publication status
Published
Review
Peer review of the complete publication
Open access category
License
Citation
Kübler, E., & Albrecht, H. (2018). Large set data mining reveals overexpressed GPCRs in prostate and breast cancer: potential for active targeting with engineered anti-cancer nanomedicines. Oncotarget, 9(38), 24882–24897. https://doi.org/10.18632/oncotarget.25427