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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Autor:innen
Albrecht, Hugo
Autor:in (Körperschaft)
Publikationsdatum
05/2018
Typ der Arbeit
Studiengang
Typ
01A - Beitrag in wissenschaftlicher Zeitschrift
Herausgeber:innen
Herausgeber:in (Körperschaft)
Betreuer:in
Übergeordnetes Werk
Oncotarget
Themenheft
DOI der Originalpublikation
Link
Reihe / Serie
Reihennummer
Jahrgang / Band
9
Ausgabe / Nummer
38
Seiten / Dauer
24882-24897
Patentnummer
Verlag / Herausgebende Institution
Impact Journals LLC
Verlagsort / Veranstaltungsort
Auflage
Version
Programmiersprache
Abtretungsempfänger:in
Praxispartner:in/Auftraggeber:in
Zusammenfassung
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.
Schlagwörter
GCPR, Pathology, cancer, meta-data, nanocarrier, targeted chemotherapy
Fachgebiet (DDC)
Veranstaltung
Startdatum der Ausstellung
Enddatum der Ausstellung
Startdatum der Konferenz
Enddatum der Konferenz
Datum der letzten Prüfung
ISBN
ISSN
1949-2553
Sprache
Englisch
Während FHNW Zugehörigkeit erstellt
Ja
Zukunftsfelder FHNW
Publikationsstatus
Veröffentlicht
Begutachtung
Peer-Review der ganzen Publikation
Open Access-Status
Lizenz
Zitation
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