TRIM24 degradation counteracts adaptation to androgen receptor inhibition in prostate cancer
The androgen receptor (AR) is the primary therapeutic target in prostate cancer. Although androgen deprivation therapy (ADT) and androgen receptor signaling inhibitors (ARSi) effectively control the disease, progression eventually leads to fatal castration-resistant prostate cancer (CRPC). However, the mechanisms underlying tumor relapse in residual disease after ADT/ARSi remain poorly understood. Recent findings reveal a critical role for TRIM24 in supporting the survival of residual cell clusters primed for tumor relapse in vivo. Reducing TRIM24 with bifunctional degraders (dTRIM24) significantly delays or even prevents the emergence of CRPC in the context of AR re-activation and lineage plasticity. In addition to inhibiting AR signaling, dTRIM24 counters adaptive pathways engaged by AR inhibition. These observations highlight TRIM24 as a promising and druggable target for preventing prostate cancer progression under AR inhibition.