The orally available multikinase inhibitor regorafenib (BAY 73-4506) in multiple myeloma
A promising approach to the treatment of multiple myeloma (MM) involves agents that target not only the myeloma cells directly, but also the tumor microenvironment which promotes tumor cell growth, angiogenesis, and MM bone disease. Here we investigate the orally available multikinase inhibitor, reg...
Gespeichert in:
| Hauptverfasser: | , , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
23 January 2018
|
| In: |
Annals of hematology
Year: 2018, Jahrgang: 97, Heft: 5, Pages: 839-849 |
| ISSN: | 1432-0584 |
| DOI: | 10.1007/s00277-018-3237-5 |
| Online-Zugang: | Verlag, Volltext: https://doi.org/10.1007/s00277-018-3237-5
|
| Verfasserangaben: | Iris Breitkreutz, Klaus Podar, Vianihuini Figueroa-Vazquez, Scott Wilhelm, Patrick J. Hayden, Kenneth C. Anderson, Marc S. Raab |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1671438817 | ||
| 003 | DE-627 | ||
| 005 | 20220816210331.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 190815s2018 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1007/s00277-018-3237-5 |2 doi | |
| 035 | |a (DE-627)1671438817 | ||
| 035 | |a (DE-599)KXP1671438817 | ||
| 035 | |a (OCoLC)1341237873 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Breitkreutz, Iris |d 1970- |e VerfasserIn |0 (DE-588)124783309 |0 (DE-627)366051806 |0 (DE-576)186798725 |4 aut | |
| 245 | 1 | 4 | |a The orally available multikinase inhibitor regorafenib (BAY 73-4506) in multiple myeloma |c Iris Breitkreutz, Klaus Podar, Vianihuini Figueroa-Vazquez, Scott Wilhelm, Patrick J. Hayden, Kenneth C. Anderson, Marc S. Raab |
| 264 | 1 | |c 23 January 2018 | |
| 300 | |a 11 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 15.08.2019 | ||
| 520 | |a A promising approach to the treatment of multiple myeloma (MM) involves agents that target not only the myeloma cells directly, but also the tumor microenvironment which promotes tumor cell growth, angiogenesis, and MM bone disease. Here we investigate the orally available multikinase inhibitor, regorafenib (BAY 73-4506), for its therapeutic efficacy in MM. Regorafenib is a potent inhibitor of angiogenic (VEGFR 1-3, PDGFR-b) as well as oncogenic (c-KIT, RET, FGFR, Raf) kinases. We show that regorafenib induces apoptosis in all MM cell lines at below clinically achievable concentrations. Regorafenib overcomes the growth advantage conferred by a stroma cell MM and an endothelial cell MM, co-culture systems, and abrogates growth factor-stimulated MEK, ERK, and AKT phosphorylation at nanomolar to micromolar concentrations. Moreover, it inhibits endothelial cell growth and tubule formation, abrogates both VEGF secretion and VEGF-induced MM cell migration, inhibits osteoclastogenesis, and shows synergistic cytotoxicity with dexamethasone, the immunomodulatory drug pomalidomide, and the p110δ inhibitor idelalisib. Most importantly, regorafenib significantly delays tumor growth in a xenograft mouse model of human MM. These results provide the rationale for further clinical evaluation of regorafenib, alone and in combination, in the treatment of MM. | ||
| 650 | 4 | |a Antiangiogenesis effects | |
| 650 | 4 | |a Cell proliferation | |
| 650 | 4 | |a Multiple myeloma | |
| 650 | 4 | |a Osteoclasts | |
| 650 | 4 | |a Regorafenib | |
| 700 | 1 | |a Figueroa Vazquez, Vianihuini |e VerfasserIn |0 (DE-588)1144392187 |0 (DE-627)1004717652 |0 (DE-576)495366331 |4 aut | |
| 700 | 1 | |a Raab, Marc-Steffen |d 1973- |e VerfasserIn |0 (DE-588)124052460 |0 (DE-627)706520998 |0 (DE-576)293998027 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Annals of hematology |d Berlin : Springer, 1991 |g 97(2018), 5, Seite 839-849 |h Online-Ressource |w (DE-627)253389852 |w (DE-600)1458429-3 |w (DE-576)072283157 |x 1432-0584 |7 nnas |a The orally available multikinase inhibitor regorafenib (BAY 73-4506) in multiple myeloma |
| 773 | 1 | 8 | |g volume:97 |g year:2018 |g number:5 |g pages:839-849 |g extent:11 |a The orally available multikinase inhibitor regorafenib (BAY 73-4506) in multiple myeloma |
| 856 | 4 | 0 | |u https://doi.org/10.1007/s00277-018-3237-5 |x Verlag |x Resolving-System |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20190815 | ||
| 993 | |a Article | ||
| 994 | |a 2018 | ||
| 998 | |g 124052460 |a Raab, Marc-Steffen |m 124052460:Raab, Marc-Steffen |d 910000 |d 910100 |e 910000PR124052460 |e 910100PR124052460 |k 0/910000/ |k 1/910000/910100/ |p 7 |y j | ||
| 998 | |g 124783309 |a Breitkreutz, Iris |m 124783309:Breitkreutz, Iris |d 910000 |d 910100 |e 910000PB124783309 |e 910100PB124783309 |k 0/910000/ |k 1/910000/910100/ |p 1 |x j | ||
| 999 | |a KXP-PPN1671438817 |e 3507150557 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"language":["eng"],"person":[{"display":"Breitkreutz, Iris","family":"Breitkreutz","role":"aut","given":"Iris"},{"role":"aut","given":"Vianihuini","display":"Figueroa Vazquez, Vianihuini","family":"Figueroa Vazquez"},{"display":"Raab, Marc-Steffen","family":"Raab","role":"aut","given":"Marc-Steffen"}],"id":{"eki":["1671438817"],"doi":["10.1007/s00277-018-3237-5"]},"relHost":[{"pubHistory":["62, 1 (Februrary 1991)-"],"note":["Gesehen am 24.04.2025","Fortsetzung der Druck-Ausgabe","Ungezählte Beil. ab 80.2001: Supplement"],"origin":[{"dateIssuedDisp":"1991-","dateIssuedKey":"1991","publisher":"Springer","publisherPlace":"Berlin ; Heidelberg ; New York"}],"title":[{"title_sort":"Annals of hematology","subtitle":"organ of: Gesellschaft für Thrombose- und Hämostaseforschung, DGHO, Deutsche Gesellschaft für Hämatologie und Onkologie e.V., ÖGHO, Österreichische Gesellschaft für Hämatologie und Onkologie","title":"Annals of hematology"}],"disp":"The orally available multikinase inhibitor regorafenib (BAY 73-4506) in multiple myelomaAnnals of hematology","type":{"media":"Online-Ressource","bibl":"periodical"},"recId":"253389852","physDesc":[{"extent":"Online-Ressource"}],"id":{"issn":["1432-0584"],"zdb":["1458429-3"],"eki":["253389852"]},"language":["eng"],"part":{"extent":"11","volume":"97","year":"2018","pages":"839-849","issue":"5","text":"97(2018), 5, Seite 839-849"},"titleAlt":[{"title":"Hematology"}]}],"recId":"1671438817","name":{"displayForm":["Iris Breitkreutz, Klaus Podar, Vianihuini Figueroa-Vazquez, Scott Wilhelm, Patrick J. Hayden, Kenneth C. Anderson, Marc S. Raab"]},"physDesc":[{"extent":"11 S."}],"type":{"media":"Online-Ressource","bibl":"article-journal"},"note":["Gesehen am 15.08.2019"],"origin":[{"dateIssuedDisp":"23 January 2018","dateIssuedKey":"2018"}],"title":[{"title_sort":"orally available multikinase inhibitor regorafenib (BAY 73-4506) in multiple myeloma","title":"The orally available multikinase inhibitor regorafenib (BAY 73-4506) in multiple myeloma"}]} | ||
| SRT | |a BREITKREUTORALLYAVAI2320 | ||