Bisphosphonate Anticancer Activity in Prostate Cancer and Other Genitourinary Cancers

Anticancer therapies have traditionally been targeted directly against cancer cell growth. However, newer treatment strategies also target the microenvironment that supports metastatic cancer cell growth. Bisphosphonates are the standard of care for maintaining bone health in patients with bone metastases from solid tumors and bone lesions from multiple myeloma, and emerging evidence supports potential anticancer activity of bisphosphonates. Zoledronic acid (ZOL), a third-generation nitrogen-containing bisphosphonate, is currently advised for reducing the risk of skeletal morbidity in patients with bone metastases from prostate cancer and other genitourinary cancers, such as renal cell carcinoma and bladder cancer. Clinical studies indicate that ZOL can normalize bone marker levels (a potential measure of skeletal disease burden), which may improve survival in patients with aggressive bone disease from prostate and other genitourinary cancers, supporting a broader therapeutic role for ZOL in genitourinary malignancies. This review examines the rationale and emerging evidence supporting the anticancer activity of bisphosphonates, especially ZOL, against prostate and other genitourinary cancers.