Combinatorial targeting of a chromatin complex comprising Dot1L, menin and the tyrosine kinase BAZ1B reveals new therapeutic vulnerability of endocrine-therapy resistant breast cancer

Estrogen receptor alpha (ERα) is a nuclear transcription factor responsible for the regulation of many cell cycle, proliferation, and differentiation genes, especially in breast tissue. Dysregulation of ERα contributes to the formation of breast cancer and is a marker used to determine whether the cancer would be responsive to endocrine therapy. However, many ERα+ breast cancers are unresponsive to endocrine therapy or develop resistance to this treatment strategy. The authors in this paper identify novel combinatorial treatment strategies targeting Dot1L, menin, and BAZ1B.