Table 1.

Examples of lung cancer therapeutic strategies that are based on bone metastases.

Experimental details	Treatment target	Observations
NSCLC patients with multiple bone metastases were treated with gefitinib.	Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI)	Treatment halted progression of bone metastasis [13]
Screening samples from NSCLC patients obtained from 52 primary sites and 75 bone metastatic sites.	RANK/RANKL/OPG	Differential expressions of RANKL, RANK, and OPG were observed [32]
Preclinical studies after intratibial implantation of NSCLC cells in SCID mice.	EGFR and RANKL	Erlotinib, a EGFR-TKI, inhibited osteolytic bone invasion in SCID mice [13]
Screening of clinical specimens obtained from NSCLC patients.	Wnt/β-catenin	Elevated expression of Dickkopf-related protein 1 (DKK1) was observed. Differentiation of osteoblast was inhibited by DKK1 [9]
Preclinical studies of injecting NSCLC cells in SCID mice.	Colony stimulating factor (CSF1)	Suppression of CSF1 resulted in significant reduction in osteolytic lesions [16]
Ectopic expression of miR-33a in A549 cell lines.	PTHrP	miR-33a expression was inversely correlated with PTHrP [27]
100 patients with resectable NSCLC and asymptomatic bone metastases were treated with zoledronic acid (ZA) and/or strontium-89 (Sr-89).	Inhibition of bone resorption	Treatment with ZA and/or Sr-89 significantly extended the time for first SRE as well as survival time. Annual incidence of SREs was reduced [64]
Preclinical injection of NSCLC cells in athymic mice. The percentage osteolytic area of femur and tibia was evaluated.	Reduction of bone resorption	Treatment with ZA significantly reduced tumor-induced osteolysis [43]
220 NSCLC patients with skeletal metastases at time of diagnosis. The patients were treated with gefitinib.	EGFR-TI	Patients treated with EGFR-TKI had significantly longer survival and achieved overall 50% protective effect [65]
Preclinical studies of implantation of NSCLC cells in athymic mice.	EGFR-TI	Erlotinib inhibited tumor-induced osteolytic invasion in bone metastasis [10]
Preclinical studies of implantation of SCLC cells in SCID mice.	Anti-PTHrP neutralizing antibody	Suppression of osteoclast activity [44]
Preclinical implantation of SCLC cells in SCID mice.	Reveromycin A that targets isoleucyl-tRNA synthetase (IleRS)	Inhibiting osteoclast-apoptosis via suppression of IleRS in osteoclasts [44]