Bisphosphonates - Mechanisms of action in multiple myeloma

C M Shipman, M J Rogers, K Vanderkerken, B Van Camp, R G G Russell, P I Croucher

Research output: Contribution to journalLiterature review

20 Citations (Scopus)

Abstract

Bisphosphonates are a class of anti-resorptive drugs, which are effective in the treatment of osteoclast-mediated bone disease, including the osteolytic bone disease, which is a major clinical feature of patients with multiple myeloma. Recently, increases in survival following treatment with pamidronate have been observed in some patients with multiple myeloma, raising the possibility that bisphosphonates may also have an anti-tumour effect. We have demonstrated that bisphosphonates can have an anti-tumour effect in human myeloma cell in vitro, and that these anti-tumour effects induced by potent nitrogen-containing bisphosphonates are a result of inhibition of enzymes of the mevalonate pathway. However, we and others have been unable to demonstrate an anti-tumour effect of the potent bisphosphonate ibandronate in vivo, using murine models of multiple myeloma. It is therefore likely that only by studying patients receiving bisphosphonates will we be able to determine whether these compounds have a clinically important anti-tumour effect.

Original languageEnglish
Pages (from-to)829-835
Number of pages7
JournalActa Oncologica
Volume39
Publication statusPublished - 2000

Keywords

  • CELLS IN-VITRO
  • MOLD DICTYOSTELIUM-DISCOIDEUM
  • MEVALONATE PATHWAY
  • OSTEOCLAST FORMATION
  • INDUCE APOPTOSIS
  • SKELETAL EVENTS
  • BONE-RESORPTION
  • CLODRONATE
  • INHIBIT
  • PAMIDRONATE

Cite this

Shipman, C. M., Rogers, M. J., Vanderkerken, K., Van Camp, B., Russell, R. G. G., & Croucher, P. I. (2000). Bisphosphonates - Mechanisms of action in multiple myeloma. Acta Oncologica, 39, 829-835.

Bisphosphonates - Mechanisms of action in multiple myeloma. / Shipman, C M ; Rogers, M J ; Vanderkerken, K ; Van Camp, B ; Russell, R G G ; Croucher, P I .

In: Acta Oncologica, Vol. 39, 2000, p. 829-835.

Research output: Contribution to journalLiterature review

Shipman, CM, Rogers, MJ, Vanderkerken, K, Van Camp, B, Russell, RGG & Croucher, PI 2000, 'Bisphosphonates - Mechanisms of action in multiple myeloma', Acta Oncologica, vol. 39, pp. 829-835.
Shipman CM, Rogers MJ, Vanderkerken K, Van Camp B, Russell RGG, Croucher PI. Bisphosphonates - Mechanisms of action in multiple myeloma. Acta Oncologica. 2000;39:829-835.
Shipman, C M ; Rogers, M J ; Vanderkerken, K ; Van Camp, B ; Russell, R G G ; Croucher, P I . / Bisphosphonates - Mechanisms of action in multiple myeloma. In: Acta Oncologica. 2000 ; Vol. 39. pp. 829-835.
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abstract = "Bisphosphonates are a class of anti-resorptive drugs, which are effective in the treatment of osteoclast-mediated bone disease, including the osteolytic bone disease, which is a major clinical feature of patients with multiple myeloma. Recently, increases in survival following treatment with pamidronate have been observed in some patients with multiple myeloma, raising the possibility that bisphosphonates may also have an anti-tumour effect. We have demonstrated that bisphosphonates can have an anti-tumour effect in human myeloma cell in vitro, and that these anti-tumour effects induced by potent nitrogen-containing bisphosphonates are a result of inhibition of enzymes of the mevalonate pathway. However, we and others have been unable to demonstrate an anti-tumour effect of the potent bisphosphonate ibandronate in vivo, using murine models of multiple myeloma. It is therefore likely that only by studying patients receiving bisphosphonates will we be able to determine whether these compounds have a clinically important anti-tumour effect.",
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T1 - Bisphosphonates - Mechanisms of action in multiple myeloma

AU - Shipman, C M

AU - Rogers, M J

AU - Vanderkerken, K

AU - Van Camp, B

AU - Russell, R G G

AU - Croucher, P I

PY - 2000

Y1 - 2000

N2 - Bisphosphonates are a class of anti-resorptive drugs, which are effective in the treatment of osteoclast-mediated bone disease, including the osteolytic bone disease, which is a major clinical feature of patients with multiple myeloma. Recently, increases in survival following treatment with pamidronate have been observed in some patients with multiple myeloma, raising the possibility that bisphosphonates may also have an anti-tumour effect. We have demonstrated that bisphosphonates can have an anti-tumour effect in human myeloma cell in vitro, and that these anti-tumour effects induced by potent nitrogen-containing bisphosphonates are a result of inhibition of enzymes of the mevalonate pathway. However, we and others have been unable to demonstrate an anti-tumour effect of the potent bisphosphonate ibandronate in vivo, using murine models of multiple myeloma. It is therefore likely that only by studying patients receiving bisphosphonates will we be able to determine whether these compounds have a clinically important anti-tumour effect.

AB - Bisphosphonates are a class of anti-resorptive drugs, which are effective in the treatment of osteoclast-mediated bone disease, including the osteolytic bone disease, which is a major clinical feature of patients with multiple myeloma. Recently, increases in survival following treatment with pamidronate have been observed in some patients with multiple myeloma, raising the possibility that bisphosphonates may also have an anti-tumour effect. We have demonstrated that bisphosphonates can have an anti-tumour effect in human myeloma cell in vitro, and that these anti-tumour effects induced by potent nitrogen-containing bisphosphonates are a result of inhibition of enzymes of the mevalonate pathway. However, we and others have been unable to demonstrate an anti-tumour effect of the potent bisphosphonate ibandronate in vivo, using murine models of multiple myeloma. It is therefore likely that only by studying patients receiving bisphosphonates will we be able to determine whether these compounds have a clinically important anti-tumour effect.

KW - CELLS IN-VITRO

KW - MOLD DICTYOSTELIUM-DISCOIDEUM

KW - MEVALONATE PATHWAY

KW - OSTEOCLAST FORMATION

KW - INDUCE APOPTOSIS

KW - SKELETAL EVENTS

KW - BONE-RESORPTION

KW - CLODRONATE

KW - INHIBIT

KW - PAMIDRONATE

M3 - Literature review

VL - 39

SP - 829

EP - 835

JO - Acta Oncologica

JF - Acta Oncologica

SN - 0284-186X

ER -