Initial in vivo testing of a multitarget kinase inhibitor, regorafenib, by the Pediatric Preclinical Testing Consortium

Douglas J. Harrison; Jonathan D. Gill; Michael E. Roth; Wendong Zhang; Beverly Teicher; Stephen Erickson; Greg Gatto; Raushan T. Kurmasheva; Peter J. Houghton; Malcolm A. Smith; Edward Anders Kolb; Richard Gorlick

doi:10.1002/pbc.28222

Initial in vivo testing of a multitarget kinase inhibitor, regorafenib, by the Pediatric Preclinical Testing Consortium

Douglas J. Harrison, Jonathan D. Gill, Michael E. Roth, Wendong Zhang, Beverly Teicher, Stephen Erickson, Greg Gatto, Raushan T. Kurmasheva, Peter J. Houghton, Malcolm A. Smith, Edward Anders Kolb, Richard Gorlick

Greehey Children's Cancer Research Institute

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

Background: Regorafenib is a small molecule multikinase inhibitor that inhibits multiple kinases including BRAF, KIT, PDGFRB, RAF, RET, and VEGFR1-3. Procedures: The in vivo anticancer effects of regorafenib were assessed in a panel of six osteosarcoma models, three rhabdomyosarcoma models, and one Ewing sarcoma model. Results: Regorafenib induced modest inhibition of tumor growth in the models evaluated. Conclusion: The overall pattern of response to regorafenib appears similar to that of the kinase inhibitor sorafenib, with pronounced slowing of tumor growth in some models, limited to the period of agent administration, being the primary treatment effect.

Original language	English (US)
Article number	e28222
Journal	Pediatric Blood and Cancer
Volume	67
Issue number	6
DOIs	https://doi.org/10.1002/pbc.28222
State	Published - Jun 1 2020

Keywords

Ewing sarcoma
multitarget kinase inhibitor
osteosarcoma
patient derived xenograft
pediatric preclinical testing consortium
rhabdomyosarcoma

ASJC Scopus subject areas

Pediatrics, Perinatology, and Child Health
Hematology
Oncology

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10.1002/pbc.28222

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Harrison, D. J., Gill, J. D., Roth, M. E., Zhang, W., Teicher, B., Erickson, S., Gatto, G., Kurmasheva, R. T., Houghton, P. J., Smith, M. A., Kolb, E. A., & Gorlick, R. (2020). Initial in vivo testing of a multitarget kinase inhibitor, regorafenib, by the Pediatric Preclinical Testing Consortium. Pediatric Blood and Cancer, 67(6), Article e28222. https://doi.org/10.1002/pbc.28222

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title = "Initial in vivo testing of a multitarget kinase inhibitor, regorafenib, by the Pediatric Preclinical Testing Consortium",

abstract = "Background: Regorafenib is a small molecule multikinase inhibitor that inhibits multiple kinases including BRAF, KIT, PDGFRB, RAF, RET, and VEGFR1-3. Procedures: The in vivo anticancer effects of regorafenib were assessed in a panel of six osteosarcoma models, three rhabdomyosarcoma models, and one Ewing sarcoma model. Results: Regorafenib induced modest inhibition of tumor growth in the models evaluated. Conclusion: The overall pattern of response to regorafenib appears similar to that of the kinase inhibitor sorafenib, with pronounced slowing of tumor growth in some models, limited to the period of agent administration, being the primary treatment effect.",

keywords = "Ewing sarcoma, multitarget kinase inhibitor, osteosarcoma, patient derived xenograft, pediatric preclinical testing consortium, rhabdomyosarcoma",

author = "Harrison, {Douglas J.} and Gill, {Jonathan D.} and Roth, {Michael E.} and Wendong Zhang and Beverly Teicher and Stephen Erickson and Greg Gatto and Kurmasheva, {Raushan T.} and Houghton, {Peter J.} and Smith, {Malcolm A.} and Kolb, {Edward Anders} and Richard Gorlick",

note = "Funding Information: This work was supported by the National Cancer Institute (Grant Nos. CA199221 and CA199222), Swim Across America, and the Foster Foundation. Regorafenib was supplied by Bayer. Funding Information: This work was supported by the National Cancer Institute (Grant Nos. CA199221 and CA199222), Swim Across America, and the Foster Foundation. Regorafenib was supplied by Bayer. Publisher Copyright: {\textcopyright} 2020 Wiley Periodicals, Inc.",

year = "2020",

month = jun,

day = "1",

doi = "10.1002/pbc.28222",

language = "English (US)",

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T1 - Initial in vivo testing of a multitarget kinase inhibitor, regorafenib, by the Pediatric Preclinical Testing Consortium

AU - Harrison, Douglas J.

AU - Gill, Jonathan D.

AU - Roth, Michael E.

AU - Zhang, Wendong

AU - Teicher, Beverly

AU - Erickson, Stephen

AU - Gatto, Greg

AU - Kurmasheva, Raushan T.

AU - Houghton, Peter J.

AU - Smith, Malcolm A.

AU - Kolb, Edward Anders

AU - Gorlick, Richard

N1 - Funding Information: This work was supported by the National Cancer Institute (Grant Nos. CA199221 and CA199222), Swim Across America, and the Foster Foundation. Regorafenib was supplied by Bayer. Funding Information: This work was supported by the National Cancer Institute (Grant Nos. CA199221 and CA199222), Swim Across America, and the Foster Foundation. Regorafenib was supplied by Bayer. Publisher Copyright: © 2020 Wiley Periodicals, Inc.

PY - 2020/6/1

Y1 - 2020/6/1

N2 - Background: Regorafenib is a small molecule multikinase inhibitor that inhibits multiple kinases including BRAF, KIT, PDGFRB, RAF, RET, and VEGFR1-3. Procedures: The in vivo anticancer effects of regorafenib were assessed in a panel of six osteosarcoma models, three rhabdomyosarcoma models, and one Ewing sarcoma model. Results: Regorafenib induced modest inhibition of tumor growth in the models evaluated. Conclusion: The overall pattern of response to regorafenib appears similar to that of the kinase inhibitor sorafenib, with pronounced slowing of tumor growth in some models, limited to the period of agent administration, being the primary treatment effect.

AB - Background: Regorafenib is a small molecule multikinase inhibitor that inhibits multiple kinases including BRAF, KIT, PDGFRB, RAF, RET, and VEGFR1-3. Procedures: The in vivo anticancer effects of regorafenib were assessed in a panel of six osteosarcoma models, three rhabdomyosarcoma models, and one Ewing sarcoma model. Results: Regorafenib induced modest inhibition of tumor growth in the models evaluated. Conclusion: The overall pattern of response to regorafenib appears similar to that of the kinase inhibitor sorafenib, with pronounced slowing of tumor growth in some models, limited to the period of agent administration, being the primary treatment effect.

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KW - patient derived xenograft

KW - pediatric preclinical testing consortium

KW - rhabdomyosarcoma

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Initial in vivo testing of a multitarget kinase inhibitor, regorafenib, by the Pediatric Preclinical Testing Consortium

Abstract

Keywords

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