Bone Targeting Agents in Patients with Metastatic Prostate Cancer: State of the Art

Abstract

Bone health represents a major issue in castration-resistant prostate cancer (CRPC) patients with bone metastases; in fact, the frequently prolonged use of hormonal agents causes important modifications in physiological bone turnover and most of these men will develop skeletal-related events (SREs), including spinal cord compression, pathologic fractures and need for surgery or radiation to bone, which are estimated to occur in almost half of this patient population. In the last decade, several novel therapeutic options have entered into clinical practice of bone metastatic CRPC, with recent approval of enzalutamide and abiraterone acetate, cabazitaxel chemotherapy and radium-223, on the basis of survival benefit suggested by landmark Phase III trials assessing these agents in this setting. Conversely, although bone-targeted agents (BTAs)—such as the bisphosphonate zoledronic acid and the receptor activator of nuclear factor kappa-B (RANK) ligand inhibitor denosumab—are approved for the prevention of SREs, these compounds have not shown benefit in terms of overall survival. However, emerging evidence has suggested that the combination of BTAs and abiraterone acetate, enzalutamide and the radiopharmaceutical radium-223 could result in improved clinical outcomes and prolonged survival in bone metastatic CRPC. In this review, we will provide an overview on bone tropism of prostate cancer and on the role of BTAs in metastatic hormone-sensitive and castration-resistant prostate cancer.

Overcoming Drug Resistance in Advanced Prostate Cancer by Drug Repurposing

“…Furthermore, despite early detection and intervention, advanced PCa might metastasize to lymph nodes and bones, lowering the quality of life and decreasing the median survival rate [ 114 ]. As a result, detecting bone metastases is crucial in clinical practice, since the beginning of bone metastasis frequently necessitates the start of chemotherapy and/or bone-targeted treatment [ 115 , 116 , 117 ]. Another point of contention in PCa care is the timing of hormonal therapy for patients with increasing PSA who have failed initial treatment, as well as if hormones can give an extra advantage to external beam radiotherapy [ 118 ].…”

Dissecting the Hormonal Signaling Landscape in Castration-Resistant Prostate Cancer

“…CRPC is frequently associated with the development of metastasis, specifically at the bone, lymph node and visceral level; a better understanding of the molecular mechanisms involved in the metastatic events associated with PCa progression might help identify novel biomarkers and possible targets to increase the therapeutic approaches against this almost untreatable disease [ 12 , 214 , 215 , 216 , 217 ].…”

Risk evaluation of denosumab and zoledronic acid for medication-related osteonecrosis of the jaw in patients with bone metastases: a propensity score–matched analysis

“…Skeletal-related events remarkably decrease the quality of life of patients with bone metastasis. Since recent progress in cancer treatments has prolonged the survival of patients with advanced cancer, the prevalence of bone metastasis in cancer patients has inevitably increased, accompanied by a further increase in the significance of corresponding treatments [3][4][5][6][7][8][9][10][11][12].…”