PRO-SENESCENCE AND SENOLYTICS
Our laboratory mainly focusses on characterizing and subsequently manipulating pathways involved in induction of senescence, as a novel therapeutic approach in treatment of PTEN-deficient prostate tumors.
Prostate cancer (PCa) at advanced stage is extremely irresponsive to conventional and targeted therapies, where chemotherapy remains of palliative benefit. These tumors often harbor PTEN-loss, which results in poor prognosis and therapy-resistance. While acute loss of PTEN induces senescence response both in vitro and in vivo, termed Pten-loss induced cellular senescence (PICS), we aim to identify novel enhancers and their target genes involved in modulating PICS. Importantly, even though senescence is demonstrated to restrict tumorigenesis in vivo, prolonged accumulation of such senescent tumor cells, have been reported to have a negative impact on the tumor microenvironment thereby allowing its progression. Thus, we aim to identify small molecule inhibitors that can selectively eliminate senescent-tumor cells. Our final aim is to implement, in tandem, a ‘Pro-senescence approach’ followed by ‘Senolytic therapy’.
Our research is focused on the characterization of a novel type of cellular senescence response which is elicited by complete loss of the tumor suppressor PTEN, and on the identification of novel compounds with pro-senescence activity. The final aim is to develop the concept of pro-senescence therapy for cancer, from experimental evidences to clinic, investigating the efficacy of “pro-senescence” compounds in phase I clinical trials. This will also allow for the identification of senescence markers in human tumor samples to be used in clinic.
- Full Professor, Department of Medicine, University of Padua, Padua, Italy (2017)
- Full Professor, USI (Università della Svizzera Italiana), Lugano, Switzerland (2017)
- Clinical Oncology Specialization, Regina Elena National Cancer Institute, Rome, Italy (2004)
- Group leader: Venetian Institute of Molecular Medicine (VIMM), Padova, Italy (since 2012)
- Medicine M.D..University of Rome “La Sapienza”, Rome, Italy (2000)
- 2015-2019, Steiner award, J.Steiner Foundation
- 2016-2019, EMBO Young Investigator Programme, EMBO (European Molecular Biology Organization)
- 2010-2013, Swiss Bridge Award, Swiss Bridge Foundation
- 2009-2010, Award in translational research, ESMO (European Society of Medical Oncology)
- Fondazione CARIPARO
- Fondazione AIRC