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’.

My 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. My 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

Our laboratory mainly focuses 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 (Berthold and Moore, 2006). These tumors often harbor PTEN-loss, which results in poor prognosis and therapy-resistance. Since 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 (Alimonti et al., 2010). Importantly, even though senescence is demonstrated to restrict tumorigenesis in vivo, prolonged accumulation of such senescent tumor cells has been reported to have a negative impact on the tumor microenvironment, thereby allowing its progression (Coppé et al., 2010; Demaria et al., 2017). Thus, we aim to identify small molecule inhibitors that can selectively eliminate senescent-tumor cells. Our final goal is to implement, in tandem, a ‘Pro-senescence approach’ followed by ‘Senolytic therapy’. Recently, we extended our interest in cellular senescence role in the context of aging-related pathologies. Indeed, cellular senescence plays a causative role in the process of aging, and anti-senescence or senolytic approaches have been proposed as promising therapeutic strategies for age-associated diseases (Baker et al., 2011; Chang et al., 2017). By taking advantage of our expertise in the field, we aim to develop novel senescence-targeting therapies for the treatment of aging-related pathologies.

ANDREA ALIMONTI

  • 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)

Selected Awards

  • 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)