In vivo evaluation of the lysine-specific demethylase (KDM1A/LSD1) inhibitor SP-2577 (Seclidemstat) against pediatric sarcoma preclinical models: A report from the Pediatric Preclinical Testing Consortium (PPTC)

Raushan T. Kurmasheva; Stephen W. Erickson; Ruolan Han; Beverly A. Teicher; Malcolm A. Smith; Michael Roth; Richard Gorlick; Peter J. Houghton

doi:10.1002/pbc.29304

In vivo evaluation of the lysine-specific demethylase (KDM1A/LSD1) inhibitor SP-2577 (Seclidemstat) against pediatric sarcoma preclinical models: A report from the Pediatric Preclinical Testing Consortium (PPTC)

Raushan T. Kurmasheva, Stephen W. Erickson, Ruolan Han, Beverly A. Teicher, Malcolm A. Smith, Michael Roth, Richard Gorlick, Peter J. Houghton

Pediatrics

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Abstract

SP-2577(Seclidemstat), an inhibitor of lysine-specific demthylase KDM1A (LSD1) that is overexpressed in pediatric sarcomas, was evaluated against pediatric sarcoma xenografts. SP-2577 (100 mg/kg/day × 28 days) statistically significantly (p <.05) inhibited growth of three of eight Ewing sarcoma (EwS), four of five rhabdomyosarcoma (RMS), and four of six osteosarcoma (OS) xenografts. The increase in EFS T/C was modest (<1.5) for all models except RMS Rh10 (EFS T/C = 2.8). There were no tumor regressions or consistent changes in dimethyl histone H3(K4), HOXM1, DAX1, c-MYC and N-MYC, or tumor histology/differentiation. SP-2577 has limited activity against these pediatric sarcoma models at the dose and schedule evaluated.

Original language	English (US)
Article number	e29304
Journal	Pediatric Blood and Cancer
Volume	68
Issue number	11
DOIs	https://doi.org/10.1002/pbc.29304
State	Published - Nov 2021

ASJC Scopus subject areas

Pediatrics, Perinatology, and Child Health
Hematology
Oncology

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Kurmasheva, R. T., Erickson, S. W., Han, R., Teicher, B. A., Smith, M. A., Roth, M., Gorlick, R., & Houghton, P. J. (2021). In vivo evaluation of the lysine-specific demethylase (KDM1A/LSD1) inhibitor SP-2577 (Seclidemstat) against pediatric sarcoma preclinical models: A report from the Pediatric Preclinical Testing Consortium (PPTC). Pediatric Blood and Cancer, 68(11), Article e29304. https://doi.org/10.1002/pbc.29304

In vivo evaluation of the lysine-specific demethylase (KDM1A/LSD1) inhibitor SP-2577 (Seclidemstat) against pediatric sarcoma preclinical models: A report from the Pediatric Preclinical Testing Consortium (PPTC). / Kurmasheva, Raushan T.; Erickson, Stephen W.; Han, Ruolan et al.
In: Pediatric Blood and Cancer, Vol. 68, No. 11, e29304, 11.2021.

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

Kurmasheva, RT, Erickson, SW, Han, R, Teicher, BA, Smith, MA, Roth, M , Gorlick, R & Houghton, PJ 2021, 'In vivo evaluation of the lysine-specific demethylase (KDM1A/LSD1) inhibitor SP-2577 (Seclidemstat) against pediatric sarcoma preclinical models: A report from the Pediatric Preclinical Testing Consortium (PPTC)', Pediatric Blood and Cancer, vol. 68, no. 11, e29304. https://doi.org/10.1002/pbc.29304

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abstract = "SP-2577(Seclidemstat), an inhibitor of lysine-specific demthylase KDM1A (LSD1) that is overexpressed in pediatric sarcomas, was evaluated against pediatric sarcoma xenografts. SP-2577 (100 mg/kg/day × 28 days) statistically significantly (p <.05) inhibited growth of three of eight Ewing sarcoma (EwS), four of five rhabdomyosarcoma (RMS), and four of six osteosarcoma (OS) xenografts. The increase in EFS T/C was modest (<1.5) for all models except RMS Rh10 (EFS T/C = 2.8). There were no tumor regressions or consistent changes in dimethyl histone H3(K4), HOXM1, DAX1, c-MYC and N-MYC, or tumor histology/differentiation. SP-2577 has limited activity against these pediatric sarcoma models at the dose and schedule evaluated.",

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AB - SP-2577(Seclidemstat), an inhibitor of lysine-specific demthylase KDM1A (LSD1) that is overexpressed in pediatric sarcomas, was evaluated against pediatric sarcoma xenografts. SP-2577 (100 mg/kg/day × 28 days) statistically significantly (p <.05) inhibited growth of three of eight Ewing sarcoma (EwS), four of five rhabdomyosarcoma (RMS), and four of six osteosarcoma (OS) xenografts. The increase in EFS T/C was modest (<1.5) for all models except RMS Rh10 (EFS T/C = 2.8). There were no tumor regressions or consistent changes in dimethyl histone H3(K4), HOXM1, DAX1, c-MYC and N-MYC, or tumor histology/differentiation. SP-2577 has limited activity against these pediatric sarcoma models at the dose and schedule evaluated.

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In vivo evaluation of the lysine-specific demethylase (KDM1A/LSD1) inhibitor SP-2577 (Seclidemstat) against pediatric sarcoma preclinical models: A report from the Pediatric Preclinical Testing Consortium (PPTC)

Abstract

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