Transcription Factor MYB as Therapeutic Target: Current Developments

Abstract

The MYB protein is a pivotal player in the cellular transcriptional network, influencing major important processes such as cell proliferation, differentiation, and apoptosis. Because of its role in oncogenesis, MYB is now a compelling target for therapeutic interventions in cancer research. This review summarizes its molecular functions and current therapeutic approaches aiming to inhibit its oncogenic activity.

Emerging role of MYB transcription factors in cancer drug resistance

“…The combination of the alkaloid berberine with oligomeric proanthocyanidines revealed synergistic antiproliferative and pro-apoptotic effects in RKO and HT-29 CRC cells based on MYB and AKT downregulation, thus indicating an important role of MYB in the eminent chemoresistance-associated PI3K-AKT signaling pathway [ 225 ] . Natural MYB-p300 inhibitors, either by direct interaction with the MYB-p300 complex or by indirect mechanisms, were summarized recently, and naphthoquinones (naphthazarin, plumbagin, and shikonin), sesquiterpenes (helenalin acetate, mexicanin, and warburganal), the triterpene celastrol, and the steroid lactone withaferin A exhibited notable effects [ 226 , 227 ] . In particular, the MYB-p300 inhibitor celastrol directly blocked the MYB-KIX (kinase-inducible domain interacting domain) interaction of the MYB-p300 complex and showed antiproliferative activity against AML cells along with prolonged survival in an AML mouse model [ 228 ] .…”