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.
