Preferential sensitivity to HDAC inhibitors in tumors with CREBBP mutation
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Preferential sensitivity to HDAC inhibitors in tumors with CREBBP mutation. / Hellwig, Malte; Merk, Daniel J; Lutz, Beat; Schüller, Ulrich.
in: CANCER GENE THER, Jahrgang 27, Nr. 5, 05.2020, S. 294-300.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Preferential sensitivity to HDAC inhibitors in tumors with CREBBP mutation
AU - Hellwig, Malte
AU - Merk, Daniel J
AU - Lutz, Beat
AU - Schüller, Ulrich
PY - 2020/5
Y1 - 2020/5
N2 - Mutations in the gene encoding for the histone acetyltransferase (HAT) CREBBP are common driver events in multiple types of human cancer, such as small cell lung cancer (SCLC) or Sonic Hedgehog medulloblastoma (SHH MB). Therefore, therapeutic options targeting such alterations are highly desired. We used human cell lines from SCLC as well as primary mouse tumor cells and genetically engineered mouse models for SHH MB to test treatment options with histone deacetylase inhibitors (HDACi) in CREBBP wild-type and mutated tumors. In contrast to CREBBP wild-type SCLC cells, CREBBP-mutated SCLC cells showed significantly lower IC50 values after treatment with HDACi. In addition, both in vitro and in vivo, HDACi had significant effects on cell proliferation of SHH-driven tumor MB cells harboring a CREBBP-mutation as compared to CREBBP wild-type controls. These data suggest that HDACi may serve as an additional therapeutic option for patients suffering from tumors driven by CREBBP mutations.
AB - Mutations in the gene encoding for the histone acetyltransferase (HAT) CREBBP are common driver events in multiple types of human cancer, such as small cell lung cancer (SCLC) or Sonic Hedgehog medulloblastoma (SHH MB). Therefore, therapeutic options targeting such alterations are highly desired. We used human cell lines from SCLC as well as primary mouse tumor cells and genetically engineered mouse models for SHH MB to test treatment options with histone deacetylase inhibitors (HDACi) in CREBBP wild-type and mutated tumors. In contrast to CREBBP wild-type SCLC cells, CREBBP-mutated SCLC cells showed significantly lower IC50 values after treatment with HDACi. In addition, both in vitro and in vivo, HDACi had significant effects on cell proliferation of SHH-driven tumor MB cells harboring a CREBBP-mutation as compared to CREBBP wild-type controls. These data suggest that HDACi may serve as an additional therapeutic option for patients suffering from tumors driven by CREBBP mutations.
U2 - 10.1038/s41417-019-0099-5
DO - 10.1038/s41417-019-0099-5
M3 - SCORING: Journal article
C2 - 31068675
VL - 27
SP - 294
EP - 300
JO - CANCER GENE THER
JF - CANCER GENE THER
SN - 0929-1903
IS - 5
ER -