The research team led by Dr. Francesco Bertoni has discovered the potential role of Bromodomain and Extra Terminal domain (BET) inhibitor birabresib (MK-8628/OTX015) in treating mantle cell lymphoma (MCL) patients, which are still in need of therapeutic improvement. Innovative results have been published in ESMO Open journal.
BET proteins act as transcriptional regulators of key signaling pathways and BET inhibitors have shown preclinical activity in different cancer models.
Tarantelli C. and Bernasconi E. demonstrated that MCL cells exposed to birabresib undergo a downregulation of important pathways, and expression changes suggest rational combinations with multiple targeted agents. The combination of birabresib with other targeted agents (i.e. pomalidomide, or inhibitors of BTK, mTOR and ATR) resulted beneficial in MCL cell lines.
Since patients with MCL needs novel therapeutic approaches, based on these results birabresib and novel drug combinations with BET inhibitor can be designed in patients affected by MCL.
BET bromodomain inhibitor birabresib in mantle cell lymphoma: in vivo activity and identification of novel combinations to overcome adaptive resistance
Chiara Tarantelli, Elena Bernasconi, Eugenio Gaudio, Luciano Cascione, Valentina Restelli, Alberto Jesus Arribas, Filippo Spriano, Andrea Rinaldi, Afua Adjeiwaa Mensah, Ivo Kwee, Maurilio Ponzoni M.D., Emanuele Zucca, Laura Carrassa, Maria E Riveiro, Keyvan Rezai, Anastasios Stathis, Esteban Cvitkovic, Francesco Bertoni