Targeting the RANKL Pathway: Putting the Brakes on Prostate Cancer Progression in Bone

摘要

The spread of prostate cancer (PC) to bone represents a critical turning point in disease progression and occurs in > 90% of lethal cases. In advanced or recurrent nonmetastatic PC, castration-based therapy is often the first line of treatment in an effort to delay metastasis and improve survival. Unfortunately, androgen-deprivation therapy is usually insufficient for durable remission, and serum prostate-specific antigen (PSA) relapse indicates progression to castration-resistant prostate cancer (CRPC). A majority of patients with CRPC develop bone metastases, which may bring a significant risk of skeletal-related events (SREs), including pathologic fractures, spinal cord compression, hypercakemia, and debilitating pain requiring irradiation or surgical intervention. Pharmacologic prevention of SREs with zoledronic acid or deno-sumab is a standard practice in metastatic CRPC; however, the benefit of such agents in metastasis prevention is still under investigation.