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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
Author(s) -
Kurmasheva Raushan T.,
Erickson Stephen W.,
Earley Eric,
Smith Malcolm A.,
Houghton Peter J.
Publication year - 2021
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.28772
Subject(s) - medicine , preclinical testing , vincristine , in vivo , irinotecan , pharmacology , cyclophosphamide , oncology , chemotherapy , cancer , medical physics , microbiology and biotechnology , colorectal cancer , biology
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.