Systematic Meta-Analysis Identifies Co-Expressed Kinases and GPCRs in Ovarian Cancer Tissues Revealing a Potential for Targeted Kinase Inhibitor Delivery
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Authors
Albrecht, Hugo
Author (Corporation)
Publication date
02.09.2019
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Type
01A - Journal article
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Parent work
Pharmaceutics
Special issue
DOI of the original publication
Series
Series number
Volume
11
Issue / Number
9
Pages / Duration
Patent number
Publisher / Publishing institution
Elsevier
Place of publication / Event location
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Abstract
The use of many anticancer drugs is problematic due to severe adverse effects. While the recent clinical launch of several kinase inhibitors led to tremendous progress, these targeted agents tend to be of non-specific nature within the kinase target class. Moreover, target mediated adverse effects limit the exploitation of some very promising kinase targets, including mitotic kinases. A future strategy will be the development of nanocarrier-based systems for the active delivery of kinase inhibitors using cancer specific surface receptors. The G-protein-coupled-receptors (GPCRs) represent the largest cell surface receptor family and some members are known to be frequently overexpressed in various cancer types. In the presented study, we used ovarian cancer tissues as an example to systematically identify concurrently overexpressed GPCRs and kinases. The rationale of this approach will guide the future design of nanoparticles, which will dock to GPCRs on cancer cells via specific ligands and deliver anticancer compounds after receptor mediated internalization. In addition to this, the approach is expected to be most effective by matching the inhibitor profiles of the delivered kinase inhibitors to the observed kinase gene expression profiles. We validated the suggested strategy in a meta-analysis, revealing overexpression of selected GPCRs and kinases in individual samples of a large ovarian cancer data set. The presented data demonstrate a large untapped potential for personalized cancer therapy using high-end targeted nanopharmaceuticals with kinase inhibitors.
Keywords
GPCR, cancer, kinase, personalized medicine, targeted drug delivery
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ISBN
ISSN
0378-5173
1873-3476
1873-3476
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
Albrecht, H., & Kübler, E. (2019). Systematic Meta-Analysis Identifies Co-Expressed Kinases and GPCRs in Ovarian Cancer Tissues Revealing a Potential for Targeted Kinase Inhibitor Delivery. Pharmaceutics, 11(9). https://doi.org/10.3390/pharmaceutics11090454.