Prevention and Management of Bone Metastases in Lung Cancer: A Review

Abstract

Approximately 30 to 40% of patients with advanced lung cancer will develop bone metastases in the course of their disease, resulting in a significant negative impact on both morbidity and survival. Skeletal complications of bone metastases include pain, pathologic fractures, spinal cord compression, and hypercalcemia. Total medical care costs are greater among patients with bone metastases who develop skeletal complications. A randomized phase III trial of the third generation bisphosphonate zoledronic acid has shown clinical benefit in the management of a subgroup of patients with bone metastases from lung cancer. Zoledronic acid treatment was associated with a reduction in both the risk of, and time to, a skeletal-related event. One of the markers of bone resorption, N-telopeptide, is both prognositic for development of skeletal-related events and predictive for benefit from zoledronic acid. In preclinical models, bisphosphonates have also demonstrated antitumor activity and are therefore currently being evaluated in adjuvant trials. Inhibition of the receptor activator of nuclear factor kappa B ligand-RANK pathway can reduce osteoclast-mediated bone resorption, and trials comparing receptor activator of nuclear factor kappa B ligand inhibitors with bisphosphonates are ongoing, including patients with lung cancer. In this article, we review the management of bone metastases and hypercalcemia as well as potential future directions for bone directed therapies in patients with lung cancer.

Identification of genes potentially involved in bone metastasis by genome-wide gene expression profile analysis of non-small cell lung cancer in mice

“…In particular, ~30-40% of patients with advanced lung cancer will develop bone metastases in the course of their disease, resulting in a significant negative impact on both morbidity and survival (3)(4)(5). Currently no curative therapy exists for bone metastasis, and clinical management is generally palliative (3,6,7). Hence, the prevention and treatment of bone metastases are clinically vital.…”

“…Most treatments for lung cancer bone metastases are proposed based on targeting the osteoclast-activating pathway, which is the key deregulation in bone metastasis in many types of cancers (3,(6)(7)(8)(9)(10). However, the cancer cells metastasizing to the bone may express certain features that mediate and favor their colonization in the bone, as well as disrupt the normal balance of bone formation and bone resorption (6,7,9).…”

“…The high mortality of this disease is predominantly due to the difficulty of early diagnosis and the highly metastatic potential of lung cancer. In many cases, metastases to multiple organs have already developed by the time of diagnosis (2)(3)(4). In particular, ~30-40% of patients with advanced lung cancer will develop bone metastases in the course of their disease, resulting in a significant negative impact on both morbidity and survival (3)(4)(5).…”

“…In many cases, metastases to multiple organs have already developed by the time of diagnosis (2)(3)(4). In particular, ~30-40% of patients with advanced lung cancer will develop bone metastases in the course of their disease, resulting in a significant negative impact on both morbidity and survival (3)(4)(5). Currently no curative therapy exists for bone metastasis, and clinical management is generally palliative (3,6,7).…”

Glabridin Inhibits Migration, Invasion, and Angiogenesis of Human Non–Small Cell Lung Cancer A549 Cells by Inhibiting the FAK/Rho Signaling Pathway

“…2 Metastasized lung cancer is particularly challenging because it is highly resistant to radiation and conventional chemotherapeutic agents. 1,2 Consequently, novel therapeutic agents are needed to deal with the increasing incidence of human lung cancer.…”