LB1763 Combinatorial BRD9 and SMO targeting synergistically suppress UV-induced BCC tumor burden in a murine model of Gorlin syndrome (GS)

Hedgehog (Hh)-targeted drugs drive tumor regression in GS patients. The efficacy of Hh inhibitors (HHi) is limited by tumor resistance/regrowth following drug discontinuation supporting the need to search for novel druggable treatment pathways. Bromodomain-containing protein 9 (BRD9) is a component of non-canonical BAF of SWI/SNF chromatin remodeling complexes. Protein kinase B/AKT enhances cell survival and drives BCC growth. Using murine ASZ001 BCC cells and Ptch1+/-/SKH1 mice, we show persistent elevation of BRD9 and AKT activity in HHi-resistant BCC cells and in tumor allografts.
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Source Type: research