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| Experimental details | Treatment target | Observations |
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| 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] |
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| 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] |
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| 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] |
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| 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] |
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| Preclinical studies of injecting NSCLC cells in SCID mice. | Colony stimulating factor (CSF1) | Suppression of CSF1 resulted in significant reduction in osteolytic lesions [16] |
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| Ectopic expression of miR-33a in A549 cell lines. | PTHrP | miR-33a expression was inversely correlated with PTHrP [27] |
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| 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] |
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| 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] |
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| 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] |
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| Preclinical studies of implantation of NSCLC cells in athymic mice. | EGFR-TI | Erlotinib inhibited tumor-induced osteolytic invasion in bone metastasis [10] |
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| Preclinical studies of implantation of SCLC cells in SCID mice. | Anti-PTHrP neutralizing antibody | Suppression of osteoclast activity [44] |
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| 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] |
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