BioCentury
ARTICLE | Distillery Therapeutics

Therapeutics: β-catenin (CTNNB1); BET bromodomain proteins

October 8, 2015 7:00 AM UTC

Studies in mice and patient samples suggest inhibiting the Wnt/CTNNB1 pathway could help treat BET bromodomain protein inhibitor-resistant AML. In BET inhibitor-resistant AML cells from patients, expression of Wnt/CTNNB1 pathway target genes was increased compared with expression in BET inhibitor-sensitive samples. In mouse xenograft models of BET inhibitor-resistant AML, a tool compound that inhibits BET plus a Wnt/CTNNB1 pathway inhibitor increased survival compared with the BET inhibitor alone. Next steps include identifying targets in the Wnt/CTNNB1 pathway and other signaling pathways that could be inhibited to sensitize leukemia cells to BET inhibitors.

Mitsubishi Tanabe Pharma Corp. and Merck & Co. Inc. have OTX015, a synthetic small molecule inhibitor of bromodomain containing 2 (BRD2), BRD3 and BRD4, in Phase II testing to treat recurrent glioblastoma multiforme (GBM) and Phase I testing to treat hematologic malignancies...