Logo Istituto Affiliato

Institute of Oncology Research (IOR),

affiliated to USI,

run by an


foundation with the same name


Research topics - Synthetic lethality between truncal mutations in SPOP and ERG in prostate cancer

The group has published a study suggesting that mutually exclusive, truncal prostate cancer driver alterations involving the ERG transcription factor and the ubiquitin ligase adaptor SPOP are antagonizing driver genes. At the molecular level, these incompatible cancer pathways are driven by opposing functions in SPOP. ERG up-regulates wild type SPOP to dampen androgen receptor (AR) signaling and sustain ERG activity through degradation of ZMYND11. Conversely, SPOP-mutant tumors stabilize ZMYND11 to repress ERG-function and enable oncogenic androgen receptor signaling. This dichotomy regulates the response to therapeutic interventions in the AR pathway. While mutant SPOP renders tumor cells susceptible to androgen deprivation therapies, ERG promotes sensitivity to high-dose androgen therapy and pharmacological inhibition of wild typeSPOP.