The research team led by Dr. Francesco Bertoni has discovered a regulatory link between BRD4, a key Bromodomain and Extra Terminal (BET) domain protein, and microRNAs, a potential magic bullet in cancer.
Afua Adjeiwaa Mensah, PhD and Luciano Cascione, PhD (Lymphoma Genomics group, Institute of Oncology Research, Bellinzona), and colleagues provide the first evidence of BET inhibitor modulation of microRNAs in lymphomas. They demonstrate that BRD4 directly modulates microRNA expression by binding to the regulatory regions of specific microRNAs, or indirectly as demonstrated for miR-96-5p, a microRNA with important functions in the proliferation and survival of B-cell malignancies.
Several drugs that inhibit BRD4 and other members of the BET family (BET inhibitors) have shown preclinical activity in different cancer models, including lymphomas, and are currently being evaluated in clinical trials with promising results. The identification of biomarkers that could be used in clinical trials to evaluate and confirm drug efficacy is a crucial aspect of the clinical development of BET inhibitors in the oncology setting.
This research, published in Hematologica, provides a rationale for the assessment of circulating miRNAs as a noninvasive way to monitor response to BET inhibitor treatment.
Bromodomain And Extra-Terminal Domain Inhibition Modulates The Expression Of Pathologically Relevant MicroRNAs In Diffuse Large B-Cell Lymphoma
Afua A. Mensah, Luciano Cascione, Eugenio Gaudio, Chiara Tarantelli, Riccardo Bomben, Elena Bernasconi, Domenico Zito, Andrea Lampis, Jens C. Hahne, Andrea Rinaldi, Anastasios Stathis, Emanuele Zucca, Ivo Kwee, Valter Gattei, Nicola Valeri, Maria E. Riveiro, Francesco Bertoni