The Effectiveness of Gefitinib on Spinal Metastases of Lung Cancer - Report of Two Cases -

Zukawa, Mineyuki; Nakano, Masato; Hirano, Naoki; Mizuhashi, Keiichi; Koike, Masahiko

doi:10.4184/asj.2008.2.2.109

Cited by 12 publications

(10 citation statements)

References 7 publications

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“…This finding is supported by in previous reports [17][18][19]. Normanno et al [19] demonstrated that gefitinib inhibits the ability of human bone marrow stromal cells to induce osteoclast differentiation by decreasing the levels of secreted macrophage colony-stimulating factor and the cell-associated receptor activator of the NF-kB ligand.…”

Section: Discussionsupporting

confidence: 80%

Prognostic factors for non-small cell lung cancer with bone metastasis at the time of diagnosis

Bae¹,

Lee²,

Kim³

et al. 2012

Lung Cancer

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Section: Discussionsupporting

confidence: 80%

Prognostic factors for non-small cell lung cancer with bone metastasis at the time of diagnosis

Bae¹,

Lee²,

Kim³

et al. 2012

Lung Cancer

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“…In spite of the antitumor activity shown by Gef both in vitro and xenograft models of breast and prostate cancers [ 19 , 20 , 21 , 22 ], phase-I/-II clinical trials on advanced BC patients treated with Gef yielded conflicting results, with little assessed clinical benefits for patients [ 8 , 23 , 24 , 25 , 26 , 27 ]. However, treatment of bone metastases with Gef has also been explored [ 28 , 29 ], based on the unexpected observation that treatment with this type of tyrosine kinase inhibitor (TKI) could relieve bone pain in BC patients [ 30 , 31 ]. Ultimately, the available data from both preclinical studies and clinical observations may pave the way for the use of Gef and other TKIs for the treatment of bone metastases.…”

Section: Introductionmentioning

confidence: 99%

Tumor-Stroma Crosstalk in Bone Tissue: The Osteoclastogenic Potential of a Breast Cancer Cell Line in a Co-Culture System and the Role of EGFR Inhibition

Mercatali

Manna

Miserocchi

et al. 2017

IJMS

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Although bone metastases represent a major challenge in the natural history of breast cancer (BC), the complex interactions involved have hindered the development of robust in vitro models. The aim of this work is the development of a preclinical model of cancer and bone stromal cells to mimic the bone microenvironment. We studied the effects on osteoclastogenesis of BC cells and Mesenchymal stem cells (MSC) cultured alone or in combination. We also analyzed: (a) whether the blockade of the Epithelial Growth Factor Receptor (EGFR) pathway modified their influence on monocytes towards differentiation, and (b) the efficacy of bone-targeted therapy on osteoclasts. We evaluated the osteoclastogenesis modulation of human peripheral blood monocytes (PBMC) indirectly induced by the conditioned medium (CM) of the human BC cell line SCP2, cultured singly or with MSC. Osteoclastogenesis was evaluated by TRAP analysis. The effect of the EGFR blockade was assessed by treating the cells with gefitinib, and analyzed with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and Western Blot (WB). We observed that SCP2 co-cultured with MSC increased the differentiation of PBMC. This effect was underpinned upon pre-treatment of the co-culture with gefitinib. Co-culture of SCP2 with MSC increased the expression of both the bone-related marker Receptor Activator of Nuclear Factor κB (RANK) and EGFR in BC cells. These upregulations were not affected by the EGFR blockade. The effects of the CM obtained by the cells treated with gefitinib in combination with the treatment of the preosteoclasts with the bone-targeted agents and everolimus enhanced the inhibition of the osteoclastogenesis. Finally, we developed a fully human co-culture system of BC cells and bone progenitor cells. We observed that the interaction of MSC with cancer cells induced in the latter molecular changes and a higher power of inducing osteoclastogenesis. We found that blocking EGFR signaling could be an efficacious strategy for breaking the interactions between cancer and bone cells in order to inhibit bone metastasis.

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“…Studies suggested that the prognosis of brain and/or bone metastases patients from NSCLC may be also associated with the status of EGFR mutations 17-20. Different EGRF mutations with different EGFR-TKI responses have also been reported in NSCLC patients with brain metastasis 21.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of Second-line Tyrosine Kinase Inhibitors in the Treatment of Metastatic Advanced Non-small-cell Lung Cancer Harboring Exon 19 and 21 EGFR Mutations

Zhao¹,

Jin²,

Lin³

et al. 2017

J. Cancer

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Background: Although superior clinical benefits of first-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in the treatment of advanced non-small-cell lung cancer (NSCLC) had been reported with different sensitivity, the sensitivity of second-line TKIs in NSCLC patients with different EFGR mutations was unknown. The purpose of this study is to investigate the clinical outcome of second-line EGFR-TKIs in the treatment of NSCLC patients according to different EGFR genotypes.Methods: The treatment outcomes of 166 NSCLC patients with different EGFR mutations treated by second-line TKIs were retrospectively reviewed. The efficacy was evaluated with Pearson chi-square or Fisher's exact tests, Log-rank test and Cox proportional hazards model.Results: The disease control rate (DCR) and objective response rate (ORR) of enrolled NSCLC patients were 77.7% and 11.4%, respectively. The exon 19 deletion group had a significantly longer median progression-free survival (PFS) (6.7 vs. 4.5 months, P=0.002) and overall survival (OS) (13.7 vs. 11.7 months, P=0.02) compared with the exon 19 L858R mutation group for NSCLC patients, as well for patients with brain metastasis [PFS: (6.7 vs. 3.9 months, p<0.001), OS: (13.7 vs. 7.9 months, p=0.006)]. No significant difference on PFS and OS was observed between exon 19 deletion and L858R mutation group for patients with bone metastasis. EGFR genotype and ECOG PS were independent predictors of PFS. Never smoking, exon 19 deletion, EGOC PS (0-1) and no brain metastasis were correlated with longer OS. No significant difference on side effect between exon 19 and 21 mutation group was observed.Conclusions: NSCLC patients harboring exon 19 deletion achieved better PFS and OS than those with L858R mutation, indicating that EGFR mutation is a significant prognostic factor for advanced NSCLC patients with and without brain metastasis receiving second-line EGFR-TKIs treatment.

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The Effectiveness of Gefitinib on Spinal Metastases of Lung Cancer - Report of Two Cases -

Cited by 12 publications

References 7 publications

Prognostic factors for non-small cell lung cancer with bone metastasis at the time of diagnosis

Prognostic factors for non-small cell lung cancer with bone metastasis at the time of diagnosis

Tumor-Stroma Crosstalk in Bone Tissue: The Osteoclastogenic Potential of a Breast Cancer Cell Line in a Co-Culture System and the Role of EGFR Inhibition

Efficacy of Second-line Tyrosine Kinase Inhibitors in the Treatment of Metastatic Advanced Non-small-cell Lung Cancer Harboring Exon 19 and 21 EGFR Mutations

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