TY - JOUR
T1 - In vivo evaluation of the lysine-specific demethylase (KDM1A/LSD1) inhibitor SP-2577 (Seclidemstat) against pediatric sarcoma preclinical models
T2 - A report from the Pediatric Preclinical Testing Consortium (PPTC)
AU - Kurmasheva, Raushan T.
AU - Erickson, Stephen W.
AU - Han, Ruolan
AU - Teicher, Beverly A.
AU - Smith, Malcolm A.
AU - Roth, Michael
AU - Gorlick, Richard
AU - Houghton, Peter J.
N1 - Publisher Copyright:
© 2021 Wiley Periodicals LLC
PY - 2021/11
Y1 - 2021/11
N2 - 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.
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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U2 - 10.1002/pbc.29304
DO - 10.1002/pbc.29304
M3 - Article
C2 - 34453478
AN - SCOPUS:85113625092
SN - 1545-5009
VL - 68
JO - Medical and Pediatric Oncology
JF - Medical and Pediatric Oncology
IS - 11
M1 - e29304
ER -