Crizotinib overcomes hepatocyte growth factor-mediated resistance to gefitinib in EGFR-mutant non-small-cell lung cancer cells

Chen, Xi; Zhou, Jianya; Zhao, Jing; Chen, Junjun; Ma, Shanni; Zhou, Jianying

doi:10.1097/cad.0000000000000011

Cited by 20 publications

(14 citation statements)

References 8 publications

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“…It is well known that the PI3K/Akt pathway plays a critical role in tumor biology (31). TLR9 agonist may promote the metastasis of human lung cancer cells via CXCR4/SDF-1/Akt pathway (29).…”

Section: Effects Of Pi3k or Akt Inhibitor On The Proliferation And MImentioning

confidence: 99%

MicroRNA-26a involved in Toll-like receptor 9-mediated lung cancer growth and migration

Jiang¹,

Wang²,

Jiang³

et al. 2014

International Journal of Molecular Medicine

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Toll-like receptor 9 (TLR9) has been shown to have a significant role in cancer. MicroRNAs (miRNAs), a group of small non-coding RNAs that fine tune translation of multiple target mRNAs, are involved in the development and progression of human cancers. The present study was undertaken to determine the roles of TLR9 on lung cancer and whether miR-26a is involved in TLR9-mediated lung cancer growth and migration. The lung cancer models were elicited by injecting human lung cancer cells into the left ventricle. The expression of TLR9 and miR-26a in lung cancer tissues obtained from lung cancer patients was increased. TLR9 ligand CpG-oligodeoxynucleotides (CpG-ODN) caused an increase in the mean tumor weight and the size of tumor mass in nude mice, and the proliferation and migration of H460 human lung cancer cells. CpG-ODN also induced an increase in the expression of miR-26a in H460 cells. The overexpression of miR-26a increased the weight and size of the tumor mass in the nude mice, and the proliferation and migration of H460 cells. Expression of phosphoinositide 3 kinase (PI3K) and phosphorylation of protein kinase B (Akt) was increased after miR-26a overexpression in the H460 cells. PI3K inhibitor wortmannin (WM) or Akt inhibitor triciribine hydrate (TCN) eliminated the increase in the proliferation and migration induced by the overexpression of miR-26a in H460 cells. These results suggested that miR-26a is involved in the TLR9-mediated growth and migration of lung cancer through the PI3K-Akt signaling pathway.

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Section: Effects Of Pi3k or Akt Inhibitor On The Proliferation And MImentioning

confidence: 99%

MicroRNA-26a involved in Toll-like receptor 9-mediated lung cancer growth and migration

Jiang¹,

Wang²,

Jiang³

et al. 2014

International Journal of Molecular Medicine

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“…Because of the role of ALK in oncogenesis, tyrosine kinase inhibition has been investigated as a therapeutic approach [11]. Crizotinib is a small-molecule selective inhibitor of ALK and mesenchymal epithelial growth factor (c-Met)/hepatocyte growth factor receptor (HGFR) kinases [12]. It was approved via accelerated drug approval by the US Food and Drug Administration in 2011, based on the findings of two early phase clinical trials demonstrating prolonged progression-free survival (PFS; 6–10 months) and high response rates (50–57%) in patients with ALK-positive NSCLC [13, 14].…”

Section: Introductionmentioning

confidence: 99%

The efficacy and safety of crizotinib in the treatment of anaplastic lymphoma kinase-positive non-small cell lung cancer: a meta-analysis of clinical trials

Qian

Gao²,

Wang

et al. 2014

BMC Cancer

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BackgroundCrizotinib was granted accelerated approval by the Food and Drug Administration in 2011 for the treatment of anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC). To evaluate the efficacy and safety of crizotinib, we performed a meta-analysis of published clinical trials using the random effect model.MethodsThe efficacy and safety of crizotinib was evaluated based on 1-year overall survival (OS), progression-free survival (PFS), overall response rate (ORR), partial response, complete response, stable disease, and dose reduction or cessation because of crizotinib toxicity.ResultsSix clinical trials were included in the meta-analysis. Crizotinib treatment demonstrated a 1-year OS of 66.8% (95% CI, 52.2–78.8%) and a PFS of 8.6 months (95% CI, 7.3–9.9 months). The aggregate ORR, partial response and complete response rates were 61.2%, 59.8% and 1.5%, respectively. The proportion of patients achieving stable disease was 42.6% (95% CI, 17.3–72.5%). The most frequently reported adverse effects of crizotinib were mild visual disturbances, nausea, vomiting, diarrhea, constipation, edema, reduction in glomerular filtration rate, and generally reversible but sometimes severe elevations in aspartate aminotransferase and alanine aminotransferase. The proportion of patients who required dose reduction or cessation because of crizotinib toxicity was 6.5% (95% CI, 4.1–10.1%).ConclusionsThis meta-analysis revealed extended survival and improved response rates in patients treated with crizotinib. As a novel, targeted anticancer agent, crizotinib appears to be a favorable treatment option for patients with locally advanced or metastatic ALK-positive NSCLC.

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“…afatinib [40,41], which may provide inhibition despite the presence of the T790M mutation), combination treatment with drugs (e.g. gefitinib plus the MET TKI crizotinib [42]) and treatment with EGFR TKIs beyond progression [43] (reviewed elsewhere [10][11][12]). However, no strategy has been approved as yet for the treatment of patients with primary or acquired resistance to gefitinib.…”

Section: Drug Resistancementioning

confidence: 99%

Gefitinib: a review of its use in adults with advanced non-small cell lung cancer

Dhillon

2015

Targ Oncol

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Gefitinib (Iressa®) is a selective small-molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (EGFR TKI) indicated for the treatment of adults with locally advanced or metastatic non-small cell lung cancer (NSCLC) with activating mutations of EGFR tyrosine kinase. Large phase III or IV clinical trials in patients with locally advanced or metastatic NSCLC showed that gefitinib as first- or subsequent-line treatment significantly prolonged progression-free survival (PFS) and improved objective response rates and/or health-related quality of life parameters in patients with activating EGFR mutations and in clinically selected patients (e.g., Asian patients or never-smokers) who are more likely to harbour these mutations. Overall survival did not increase significantly with gefitinib, although post-study treatments may have had a confounding effect on this outcome. Gefitinib was generally well tolerated in these studies, with mild or moderate skin reactions, gastrointestinal disturbances and elevations in liver enzymes among the most common adverse reactions in gefitinib recipients; interstitial lung disease has also been reported in <6 % of gefitinib recipients. Compared with chemotherapy, gefitinib as first- or subsequent-line therapy provided similar or greater PFS benefit and was generally associated with fewer haematological adverse events, neurotoxicity, asthenic disorders, as well as grade ≥3 adverse events. Although the position of gefitinib with respect to other EGFR TKIs is not definitively established, current evidence indicates that gefitinib monotherapy is an effective and generally well-tolerated first- or subsequent-line treatment option for patients with NSCLC and activating EGFR mutations who have not received an EGFR TKI previously.

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Crizotinib overcomes hepatocyte growth factor-mediated resistance to gefitinib in EGFR-mutant non-small-cell lung cancer cells

Cited by 20 publications

References 8 publications

MicroRNA-26a involved in Toll-like receptor 9-mediated lung cancer growth and migration

MicroRNA-26a involved in Toll-like receptor 9-mediated lung cancer growth and migration

The efficacy and safety of crizotinib in the treatment of anaplastic lymphoma kinase-positive non-small cell lung cancer: a meta-analysis of clinical trials

Gefitinib: a review of its use in adults with advanced non-small cell lung cancer

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