Bisphosphonates are extensively used to treat cancer-induced bone disease in
a range of solid and bone derived tumours, where they reduce the incidence of skeletal
related events and improve patients’ quality of life. Recent reports indicate that
bisphosphonates may also prevent recurrence of breast cancer at peripheral sites,
suggesting that these drugs may have anti-cancer activity outside the skeleton and
effects on a range of tumour cell types have been reported in vitro. These positive
results have subsequently been supported by investigations of effects of
bisphosphonates on tumour growth in vivo, both in bone and at peripheral sites. A
reduction of tumour burden and in cancer-induced bone disease following
bisphosphonate treatment is demonstrated in several model systems, including breast
and prostate cancer, osteosarcoma and multiple myeloma. In addition, bisphosphonates
have been shown to significantly reduce growth of human tumour cells implanted
subcutaneously in immunocompromised mice. However, the majority of in vivo studies
reporting anti-tumour effects have used high doses and frequent administration of
bisphosphonates, and the clinical relevance of these data have therefore been the subject
of considerable debate. Bisphosphonates may hold greater promise as anti-tumour
agents when used in combination with cytotoxic drugs, and several in vivo studies have
reported substantial increased inhibition of tumour growth and improved survival when
bisphosphonates have been added to standard chemotherapy regimens. This review will
summarise the published data on anti-tumour effects of bisphosphonates reported from
in vivo models, alone and in combination with other anti-cancer agents, and highlight
the main lessons learned and future challenges in this field.
Keywords: Bone metastases, breast cancer, cancer-induced bone disease, prostate
cancer.
