El-Amm Joelle, Aragon-Ching Jeanny B
The Lebanese American University, Department of Hematology and Oncology, Division of Internal Medicine, Beirut, Lebanon.
Clinical Program Director of Genitourinary Cancers, Inova Dwight and Martha Schar Cancer Institute, Fairfax, VA, USA.
Clin Med Insights Oncol. 2016 Mar 23;10(Suppl 1):11-9. doi: 10.4137/CMO.S30751. eCollection 2016.
Skeletal involvement in metastatic castrate-resistant prostate cancer (mCRPC) is common and results in significant morbidity and mortality. The interaction of prostate cancer with the bone microenvironment contributes to progression of cancer in the bone leading to skeletal-related events (SREs). Studies aimed at targeting the bone have been carried out over the recent years. Bisphosphonates are synthetic pyrophosphate analogs first investigated for their role in SRE prevention with zoledronic acid as the main bisphosphonate that is approved by the US Food and Drug Administration for retardation of skeletal events in men with metastatic prostate cancer. Denosumab is another bone-targeted agent against uncontrolled osteolysis and serves as a RANK ligand inhibitor, superior to zoledronic acid in delaying SREs. Radiopharmaceuticals have played a role in targeting the bone microenvironment mainly in pain palliation in mCRPC utilizing strontium or samarium in the remote past, but only radium-223 is the first radiopharmaceutical that has yielded improvement in overall survival. The combination and sequencing strategies of these agents is the subject of multiple ongoing trials to guide the best use of these emerging agents.
骨骼受累在转移性去势抵抗性前列腺癌（mCRPC）中很常见，并导致显著的发病率和死亡率。前列腺癌与骨微环境的相互作用促进了骨内癌症的进展，导致骨相关事件（SREs）。近年来开展了针对骨骼的研究。双膦酸盐是合成的焦磷酸盐类似物，最初研究其在预防SREs中的作用，唑来膦酸是主要的双膦酸盐，已被美国食品药品监督管理局批准用于延缓转移性前列腺癌男性的骨骼事件。地诺单抗是另一种针对不受控制的骨溶解的骨靶向药物，作为一种核因子κB受体活化因子配体抑制剂，在延缓SREs方面优于唑来膦酸。放射性药物主要在过去利用锶或钐缓解mCRPC的疼痛方面在靶向骨微环境中发挥了作用，但只有镭-223是第一种能提高总生存率的放射性药物。这些药物的联合和序贯策略是多个正在进行的试验的主题，以指导这些新兴药物的最佳使用。
