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Review
. 2015 Jul;7(4):219-28.
doi: 10.1177/1758834015582178.

Bone-targeted agents in the treatment of lung cancer

Shobha C Silva  1 , Caroline Wilson  1 , Penella J Woll  2
Affiliations
Review

Bone-targeted agents in the treatment of lung cancer

Shobha C Silva et al. Ther Adv Med Oncol. 2015 Jul.

Abstract

Over a third of patients with lung cancer will develop bone metastases during the course of their disease, resulting in symptoms of pain and immobility, and skeletal-related events (SREs) such as fracture, hypercalcaemia, surgery or radiotherapy to bones, and malignant spinal cord compression. These reduce quality of life and increase mortality. Preclinical research has identified the interactions between tumour cells and bone that are key to tumour cell survival and associated osteolysis. These data have led to the development of drugs to prevent osteoclast-mediated bone breakdown, such as zoledronic acid and denosumab, which are now licensed for use in patients with bone metastases from solid tumours. Both zoledronic acid and denosumab reduce the risk of SREs and increase time to first SRE, with minimal side effects. In addition, denosumab improved survival in patients with lung cancer compared with zoledronic acid. Ongoing trials are testing whether these drugs can prevent the development of bone metastases from lung cancer. New bone-targeted agents showing promise in breast and prostate cancer include radium-223, cabozantinib and Src inhibitors. These agents require further evaluation in patients with lung cancer.

Keywords: denosumab; skeletal-related events; survival outcomes; vicious cycle; zoledronic acid.

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Conflict of interest statement

Conflict of interest statement: The authors declare no conflicts of interest in preparing this article.

Figures

Figure 1.
Figure 1.
The vicious cycle of bone metastases. Once tumour cells arrive in bone they interact with the bone forming osteoblasts (Ob) and bone-resorbing osteoclasts (Oc). Tumour cells secrete factors that stimulate Oc, that is, parathyroid-related protein (PTHrP). The increase in osteoclast bone resorption releases growth factors such as transforming growth factor β (TGFβ) which are stored in bone matrix which further increase tumour secretion of PTHrP. Other tumour-secreted factors such as bone morphogenetic proteins (BMPs) activate osteoblasts directly which subsequently release more receptor activator of nuclear factor κβ ligand (RANKL) and less osteoprotegerin (OPG), a RANKL decoy, to initiate osteoclast differentiation and hence further bone resorption.
See this image and copyright information in PMC

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