In vivo evaluation of the EZH2 inhibitor (EPZ011989) alone or in combination with standard of care cytotoxic agents against pediatric malignant rhabdoid tumor preclinical models—A report from the Pediatric Preclinical Testing Consortium

Raushan T. Kurmasheva; Stephen W. Erickson; Eric Earley; Malcolm A. Smith; Peter J. Houghton

doi:10.1002/pbc.28772

In vivo evaluation of the EZH2 inhibitor (EPZ011989) alone or in combination with standard of care cytotoxic agents against pediatric malignant rhabdoid tumor preclinical models—A report from the Pediatric Preclinical Testing Consortium

Raushan T. Kurmasheva, Stephen W. Erickson, Eric Earley, Malcolm A. Smith, Peter J. Houghton

Greehey Children's Cancer Research Institute

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

11 Scopus citations

Abstract

The Pediatric Preclinical Testing Program (PPTP) previously reported the activity of the EZH2 inhibitor tazemetostat (EPZ6438) against xenograft models of rhabdoid tumors. Here, we determined whether an inhibitor of EZH2 enhanced the effect of standard of care chemotherapeutic agents: irinotecan, vincristine, and cyclophosphamide. EPZ011989 significantly prolonged time to event in all the six rhabdoid models studied but did not induce tumor regression. The addition of EPZ011989 to standard of care agents significantly improved time to event in at least one model for each of the agents studied, although this effect was observed in only a minority of the combination testing experiments.

Original language	English (US)
Article number	e28772
Journal	Pediatric Blood and Cancer
Volume	68
Issue number	2
DOIs	https://doi.org/10.1002/pbc.28772
State	Published - Feb 2021

Keywords

pediatric cancer
rhabdomyosarcoma
xenograft models

ASJC Scopus subject areas

Pediatrics, Perinatology, and Child Health
Hematology
Oncology

Access to Document

10.1002/pbc.28772

Fingerprint

Dive into the research topics of 'In vivo evaluation of the EZH2 inhibitor (EPZ011989) alone or in combination with standard of care cytotoxic agents against pediatric malignant rhabdoid tumor preclinical models—A report from the Pediatric Preclinical Testing Consortium'. Together they form a unique fingerprint.

Cite this

Kurmasheva, R. T., Erickson, S. W., Earley, E., Smith, M. A., & Houghton, P. J. (2021). In vivo evaluation of the EZH2 inhibitor (EPZ011989) alone or in combination with standard of care cytotoxic agents against pediatric malignant rhabdoid tumor preclinical models—A report from the Pediatric Preclinical Testing Consortium. Pediatric Blood and Cancer, 68(2), Article e28772. https://doi.org/10.1002/pbc.28772

In vivo evaluation of the EZH2 inhibitor (EPZ011989) alone or in combination with standard of care cytotoxic agents against pediatric malignant rhabdoid tumor preclinical models—A report from the Pediatric Preclinical Testing Consortium. / Kurmasheva, Raushan T.; Erickson, Stephen W.; Earley, Eric et al.
In: Pediatric Blood and Cancer, Vol. 68, No. 2, e28772, 02.2021.

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

Kurmasheva, RT, Erickson, SW, Earley, E, Smith, MA & Houghton, PJ 2021, 'In vivo evaluation of the EZH2 inhibitor (EPZ011989) alone or in combination with standard of care cytotoxic agents against pediatric malignant rhabdoid tumor preclinical models—A report from the Pediatric Preclinical Testing Consortium', Pediatric Blood and Cancer, vol. 68, no. 2, e28772. https://doi.org/10.1002/pbc.28772

Kurmasheva RT, Erickson SW, Earley E, Smith MA, Houghton PJ. In vivo evaluation of the EZH2 inhibitor (EPZ011989) alone or in combination with standard of care cytotoxic agents against pediatric malignant rhabdoid tumor preclinical models—A report from the Pediatric Preclinical Testing Consortium. Pediatric Blood and Cancer. 2021 Feb;68(2):e28772. doi: 10.1002/pbc.28772

@article{2c2356503cd44c099c1709f7bc656f3e,

title = "In vivo evaluation of the EZH2 inhibitor (EPZ011989) alone or in combination with standard of care cytotoxic agents against pediatric malignant rhabdoid tumor preclinical models—A report from the Pediatric Preclinical Testing Consortium",

abstract = "The Pediatric Preclinical Testing Program (PPTP) previously reported the activity of the EZH2 inhibitor tazemetostat (EPZ6438) against xenograft models of rhabdoid tumors. Here, we determined whether an inhibitor of EZH2 enhanced the effect of standard of care chemotherapeutic agents: irinotecan, vincristine, and cyclophosphamide. EPZ011989 significantly prolonged time to event in all the six rhabdoid models studied but did not induce tumor regression. The addition of EPZ011989 to standard of care agents significantly improved time to event in at least one model for each of the agents studied, although this effect was observed in only a minority of the combination testing experiments.",

keywords = "pediatric cancer, rhabdomyosarcoma, xenograft models",

author = "Kurmasheva, {Raushan T.} and Erickson, {Stephen W.} and Eric Earley and Smith, {Malcolm A.} and Houghton, {Peter J.}",

note = "Funding Information: We thank Abhik Bandyophadhyay, Vanessa Del Pozo, Samson Ghilu, and Edward Favours for technical assistance, and we thank Epizyme for provision of EPZ011989. This work was supported by NCI Grants: UO1 CA199297, U01 CA199222, and P30 CA054174. Publisher Copyright: {\textcopyright} 2020 Wiley Periodicals LLC",

year = "2021",

month = feb,

doi = "10.1002/pbc.28772",

language = "English (US)",

volume = "68",

journal = "Pediatric Blood and Cancer",

issn = "1545-5009",

publisher = "Wiley-Liss Inc.",

number = "2",

}

TY - JOUR

T1 - In vivo evaluation of the EZH2 inhibitor (EPZ011989) alone or in combination with standard of care cytotoxic agents against pediatric malignant rhabdoid tumor preclinical models—A report from the Pediatric Preclinical Testing Consortium

AU - Kurmasheva, Raushan T.

AU - Erickson, Stephen W.

AU - Earley, Eric

AU - Smith, Malcolm A.

AU - Houghton, Peter J.

N1 - Funding Information: We thank Abhik Bandyophadhyay, Vanessa Del Pozo, Samson Ghilu, and Edward Favours for technical assistance, and we thank Epizyme for provision of EPZ011989. This work was supported by NCI Grants: UO1 CA199297, U01 CA199222, and P30 CA054174. Publisher Copyright: © 2020 Wiley Periodicals LLC

PY - 2021/2

Y1 - 2021/2

N2 - The Pediatric Preclinical Testing Program (PPTP) previously reported the activity of the EZH2 inhibitor tazemetostat (EPZ6438) against xenograft models of rhabdoid tumors. Here, we determined whether an inhibitor of EZH2 enhanced the effect of standard of care chemotherapeutic agents: irinotecan, vincristine, and cyclophosphamide. EPZ011989 significantly prolonged time to event in all the six rhabdoid models studied but did not induce tumor regression. The addition of EPZ011989 to standard of care agents significantly improved time to event in at least one model for each of the agents studied, although this effect was observed in only a minority of the combination testing experiments.

AB - The Pediatric Preclinical Testing Program (PPTP) previously reported the activity of the EZH2 inhibitor tazemetostat (EPZ6438) against xenograft models of rhabdoid tumors. Here, we determined whether an inhibitor of EZH2 enhanced the effect of standard of care chemotherapeutic agents: irinotecan, vincristine, and cyclophosphamide. EPZ011989 significantly prolonged time to event in all the six rhabdoid models studied but did not induce tumor regression. The addition of EPZ011989 to standard of care agents significantly improved time to event in at least one model for each of the agents studied, although this effect was observed in only a minority of the combination testing experiments.

KW - pediatric cancer

KW - rhabdomyosarcoma

KW - xenograft models

UR - http://www.scopus.com/inward/record.url?scp=85093819389&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85093819389&partnerID=8YFLogxK

U2 - 10.1002/pbc.28772

DO - 10.1002/pbc.28772

M3 - Article

C2 - 33089597

AN - SCOPUS:85093819389

SN - 1545-5009

VL - 68

JO - Pediatric Blood and Cancer

JF - Pediatric Blood and Cancer

IS - 2

M1 - e28772

ER -

In vivo evaluation of the EZH2 inhibitor (EPZ011989) alone or in combination with standard of care cytotoxic agents against pediatric malignant rhabdoid tumor preclinical models—A report from the Pediatric Preclinical Testing Consortium

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this