MET inhibitors for targeted therapy of EGFR TKI-resistant lung cancer

Wang, Qiming; Yang, Sen; Wang, Kai; Sun, Shi-Yong

doi:10.1186/s13045-019-0759-9

Cited by 171 publications

(139 citation statements)

References 49 publications

(64 reference statements)

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“…e third-generation of EGFR-TKIs were designed to covalently bind only to mutated forms of EGFR, thus lowering the incidence of EGFR-TKI-mediated toxicities at wild-type receptors [2]. Nonetheless, some patients have developed resistance to the firstto third-generation EGFR-TKIs, and these patients demonstrate a high level of c-Met amplification or c-Met protein overexpression/hyperactivation [1,3]. erefore, combination therapy with EGFR-TKIs and a c-Met inhibitor is required for patients with resistant NSCLC cells carrying c-Met amplification and/or protein hyperactivation.…”

Section: Introductionmentioning

confidence: 99%

Effect of Ephedra Herb on Erlotinib Resistance in c-Met-Overexpressing Non-Small-Cell Lung Cancer Cell Line, H1993, through Promotion of Endocytosis and Degradation of c-Met

Hyuga

Amakura

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs) are used to treat non-small-cell lung cancer (NSCLC), harboring an EGFR-activating mutation. However, acquired resistance to these treatments emerges after a few years. One of causes of resistance to EGFR-TKIs is a high level of c-Met amplification or c-Met protein overexpression/hyperactivation. Therefore, combination therapy with EGFR-TKIs and a c-Met inhibitor is thought to be effective treatment for patients with NSCLC resistance carrying c-Met amplification and/or protein hyperactivation. Ephedra Herb is a crude drug and is used in Japan as a component in many Kampo formulae. We previously reported that Ephedra Herb extract (EHE) inhibits HGF-induced phosphorylation of c-Met by preventing c-Met tyrosine kinase activity. Thus, we investigated the combination effect of EHE and erlotinib, an EGFR-TKI, on growth of H1993 cells, an erlotinib-resistant NSCLC cell line with overexpression of c-Met. The EHE and erlotinib combination proved to be effective in suppression of the growth of H1993 xenograft tumors and on inhibition of proliferation of H1993 cells, suggesting that EHE is effective in rescuing NSCLC cells from erlotinib resistance. Moreover, EHE not only inhibited the phosphorylation of c-Met, but also downregulated the expression of c-Met by facilitating clathrin-mediated endocytosis and lysosomal degradation of c-Met. EHE also promoted downregulation of the expression of EGFR and phosphorylation of EGFR. Ephedrine alkaloids-free Ephedra Herb extract (EFE) had the same effects as EHE, and the 40% MeOH fraction from EFE, which mainly contained the high-molecular mass condensed tannins, decreased the expression levels of c-Met, pMet, EGFR, and pEGFR to almost the same level as EFE. These results suggest that recovery from resistance to erlotinib by EHE is derived from the high-molecular mass condensed tannins and that EHE may be suitable for treatment of c-Met-overexpressing NSCLC with resistance to EGFR-TKIs.

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Section: Introductionmentioning

confidence: 99%

Effect of Ephedra Herb on Erlotinib Resistance in c-Met-Overexpressing Non-Small-Cell Lung Cancer Cell Line, H1993, through Promotion of Endocytosis and Degradation of c-Met

Hyuga

Amakura

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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“…The c-MET gene mutation is an important mechanism and is detectable in 5-22% of NSCLCs (ref. 47 ). Constitutevely activated MET, receptor tyrosine kinase, promotes tumor angiogenesis, cell invasion and metastasis propagation in NSCLC (ref.…”

Section: Clinical Biomarkers Currently Used In Therapeutic Strategiesmentioning

confidence: 99%

Gene rearrangement detection by next-generation sequencing in patients with non-small cell lung carcinoma

Brisudova¹,

Škarda²

2020

BIOMED PAP

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Non-small cell lung carcinoma (NSCLC) is the leading cause of cancer-related deaths worldwide. Various molecular markers in NSCLC patients have been developed, including gene rearrangements, currently used in therapeutic strategies. With increasing number of these molecular biomarkers of NSCLC, there is a demand for highly efficient methods for detecting mutations and translocations in treatable targets. Those currently available U.S. Food and Drug Administration (FDA) approved approaches, for example imunohistochemisty (IHC) and fluorescence in situ hybridization (FISH), are inadequate, due to sufficient quantity of material and long time duration. Next-generation massive parallel sequencing (NGS), with the ability to perform and capture data from millions of sequencing reactions simultaneously could resolve the problem. Thanks to gradual NGS introduction into clinical laboratories, screening time should be considerably shorter, which is very important for patients with advanced NSCLC. Moreover, only a minimum sample input is needed for achieving adequate results. NGS was compared to the current detection methods of ALK, ROS1, c-RET and c-MET rearrangements in NSCLC and a significant match, between IHC, FISH and NGS results, was found. Recent available researches have been carried out on a small numbers of patients. Verifying these results on larger patients cohort is important. This review sumarizes the literature on this subject and compares current possibilities of predictive gene rearrangements detection in patients with NSCLC.

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“…Recently, FLT3 inhibitors and inhibitors of isocitrate dehydrogenases (IDH1 and IDH2) significantly enhanced the armamentarium for AML therapy [31][32][33][34][35]. TKIs targeting a variety of oncoproteins, such as EGFR, ALK, HER2, FGFR, VEGFR, RET, MET, to name a few, have brought revolutions in the therapy of non-small cell lung cancer, breast cancer, bladder cancer, liver cancer, and renal cell carcinoma [5,6,[36][37][38][39][40][41][42]. BRAF inhibitors targeting serine /threonine kinases lead to major advances in the therapy of malignant melanoma [43,44].…”

Section: Small Molecule Inhibitors (Smi) As Targeted Agents: Small Pimentioning

confidence: 99%

CAR-T “the living drugs”, immune checkpoint inhibitors, and precision medicine: a new era of cancer therapy

Liu

2019

J Hematol Oncol

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New advances in the design and manufacture of monoclonal antibodies, bispecific T cell engagers, and antibodydrug conjugates make the antibody-directed agents more powerful with less toxicities. Small molecule inhibitors are routinely used now as oral targeted agents for multiple cancers. The discoveries of PD1 and PD-L1 as negative immune checkpoints for T cells have led to the revolution of modern cancer immunotherapy. Multiple agents targeting PD1, PD-L1, or CTLA-4 are widely applied as immune checkpoint inhibitors (ICIs) which alleviate the suppression of immune regulatory machineries and lead to immunoablation of once highly refractory cancers such as stage IV lung cancer. Tisagenlecleucel and axicabtagene ciloleucel are the two approved CD19-targeted chimeric antigen receptor (CAR) T cell products. Several CART cell platforms targeting B cell maturation antigen (BCMA) are under active clinical trials for refractory and/or relapsed multiple myeloma. Still more targets such as CLL-1, EGFR, NKG2D and mesothelin are being directed in CART cell trials for leukemia and solid tumors. Increasing numbers of novel agents are being studied to target cancer-intrinsic oncogenic pathways as well as immune checkpoints. One such an example is targeting CD47 on macrophages which represents a "do-not-eat-me" immune checkpoint. Fueling the current excitement of cancer medicine includes also TCR-T cells, TCR-like antibodies, cancer vaccines and oncolytic viruses.

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MET inhibitors for targeted therapy of EGFR TKI-resistant lung cancer

Cited by 171 publications

References 49 publications

Effect of Ephedra Herb on Erlotinib Resistance in c-Met-Overexpressing Non-Small-Cell Lung Cancer Cell Line, H1993, through Promotion of Endocytosis and Degradation of c-Met

Effect of Ephedra Herb on Erlotinib Resistance in c-Met-Overexpressing Non-Small-Cell Lung Cancer Cell Line, H1993, through Promotion of Endocytosis and Degradation of c-Met

Gene rearrangement detection by next-generation sequencing in patients with non-small cell lung carcinoma

CAR-T “the living drugs”, immune checkpoint inhibitors, and precision medicine: a new era of cancer therapy

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