Università della Svizzera italiana

Hitting the right spot : mechanism of action of OPB‐31121, a novel and potent inhibitor of the Signal Transducer and Activator of Transcription 3 (STAT3)

Brambilla, Lara ; Genini, Davide ; Laurini, Erik ; Merulla, Jessica ; Perez, Laurent ; Fermeglia, Maurizio ; Carbone, Giuseppina M. ; Pricl, Sabrina ; Catapano, Carlo V.

In: Molecular oncology, 2015, vol. 9, no. 6, p. 1194-1206

STAT3 is a key element in many oncogenic pathways and, like other transcription factors, is an attractive target for development of novel anticancer drugs. However, interfering with STAT3 functions has been a difficult task and very few small molecule inhibitors have made their way to the clinic. OPB‐31121, an anticancer compound currently in clinical trials, has been reported to affect...

Università della Svizzera italiana

Mitochondrial dysfunction induced by a SH2 domain-targeting STAT3 inhibitor leads to metabolic synthetic lethality in cancer cells

Genini, Davide ; Brambilla, Lara ; Laurini, Erik ; Merulla, Jessica ; Civenni, Gianluca ; Pandit, Shusil ; D'Antuono, Rocco ; Perez, Laurent ; Levy, David E. ; Pricl, Sabrina ; Carbone, Giuseppina M. ; Catapano, Carlo V.

In: Proceedings of the national academy of sciences of the United States of America, 2017, vol. 114, no. 25, p. E4924-E4933

In addition to its canonical role in nuclear transcription, signal transducer and activator of transcription 3 (STAT3) is emerging as an important regulator of mitochondrial function. Here, we demonstrate that a novel inhibitor that binds with high affinity to the STAT3 SH2 domain triggers a complex cascade of events initiated by interference with mitochondrial STAT3 (mSTAT3). The...

Université de Fribourg

Understanding apoptosis involved in the development and treatment of malignancies

Genini, Davide ; Rusconi, Sandro (Dir.) ; Martinou, Jean-Claude (Codir.) ; Leoni, Lorenzo (Codir.)

Thèse de doctorat : Université de Fribourg, 2000 ; nr. 1321.

Apoptosis is a key event occurring in living organisms. In order to maintain tissue homeostasis, a comparable number of cells have to die to compensate for the cells produced by mitosis. However in many diseases this mechanism is altered. Once a malignancy is established, the conventional approach is to treat cells with drugs able to induce apoptosis. Although the execution of apoptosis is a...