Lenvatinib plus EGFR inhibition for liver cancer

Hindson, Jordan

doi:10.1038/s41575-021-00513-6

Cited by 9 publications

(12 citation statements)

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“…The melting points of the known intermediates were compared with the literature. The structures of the synthesized compounds were characterized by FT-IR, 1 H-NMR, 13 C-NMR (APT), and HR-MS spectroscopic methods.…”

Section: Chemistrymentioning

confidence: 99%

“…The FT-IR spectra of the compounds were recorded using ALPHA-P BRUKER FT-IR Spectrophotometer. 1 H-NMR and 13 C-NMR (APT) spectra were recorded on Bruker Avance NEO 500 and 125 MHz NMR spectrometer. Chemical shifts were reported as δ in ppm relative to tetramethylsilane (TMS) (δ 0.00 singlet) in deuterated dimethyl sulfoxide ((D 6 )DMSO) and deuterated chloroform (CDCl 3 ).…”

Section: Experimental Section Synthesismentioning

confidence: 99%

“…However, the effectiveness of these therapies can be limited by the development of resistance mechanisms, such as secondary mutations or alternative signaling pathways. Therefore, there is ongoing research to identify new strategies to overcome resistance and improve the efficacy of EGFR‐targeted therapies in cancer treatment [13,14] . EGFR signaling has also been implicated in the pathogenesis of several inflammatory disorders, such as asthma, chronic obstructive pulmonary disease and inflammatory bowel disease [15] …”

Section: Introductionmentioning

confidence: 99%

“…Therefore, there is ongoing research to identify new strategies to overcome resistance and improve the efficacy of EGFRtargeted therapies in cancer treatment. [13,14] EGFR signaling has also been implicated in the pathogenesis of several inflammatory disorders, such as asthma, chronic obstructive pulmonary disease and inflammatory bowel disease. [15] Molecular docking is a method that predicts the binding orientation and affinity of a ligand (a small molecule) to a protein receptor.…”

Section: Introductionmentioning

confidence: 99%

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New Anthranilic Acid Hydrazones as Fenamate Isosteres: Synthesis, Characterization, Molecular Docking, Dynamics & in Silico ADME, in Vitro Anti‐Inflammatory and Anticancer Activity Studies

Şenol

Cagman

Katmerlikaya

et al. 2023

Chemistry & Biodiversity

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In this study, twenty new anthranilic acid hydrazones 6–9 (a–e) were synthesized and their structures were characterized by Fourier‐transform Infrared (FT‐IR), Nuclear Magnetic Resonance (1H‐NMR – 13C‐NMR), and High‐resolution Mass Spectroscopy (HR‐MS). The inhibitory effects of the compounds against COX‐II were evaluated. IC50 values of the compounds were found in the range of >200–0.32 μM and compounds 6e, 8d, 8e, 9b, 9c, and 9e were determined to be the most effective inhibitors. Cytotoxic effects of the most potent compounds were investigated against human hepatoblastoma (Hep‐G2) and human healthy embryonic kidney (Hek‐293) cell lines. Doxorubicin (IC50: 8.68±0.16 μM for Hep‐G2, 55.29±0.56 μM for Hek‐293) was used as standard. 8e is the most active compound, with low IC50 against Hep‐G2 (4.80±0.04 μM), high against Hek‐293 (159.30±3.12), and high selectivity (33.15). Finally, molecular docking and dynamics studies were performed to understand ligand‐protein interactions between the most potent compounds and COX II, Epidermal Growth Factor Receptor (EGFR), and Transforming Growth Factor beta II (TGF‐βII). The docking scores were calculated in the range of −10.609–−6.705 kcal/mol for COX‐II, −8.652–−7.743 kcal/mol for EGFR, and −10.708–−8.596 kcal/mol for TGF‐βII.

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Section: Chemistrymentioning

confidence: 99%

Section: Experimental Section Synthesismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

New Anthranilic Acid Hydrazones as Fenamate Isosteres: Synthesis, Characterization, Molecular Docking, Dynamics & in Silico ADME, in Vitro Anti‐Inflammatory and Anticancer Activity Studies

Şenol

Cagman

Katmerlikaya

et al. 2023

Chemistry & Biodiversity

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“…Liver cancer is an aggressive tumor, and its incidence is increasing globally (1). Hepatocellular carcinoma (HCC), accounting for more than 90% of the total cases of primary liver cancer, is the sixth most common type of cancer, and the fourth most common cause of cancer-associated deaths worldwide (2).…”

Section: Introductionmentioning

confidence: 99%

SPC25 promotes hepatocellular carcinoma metastasis via activating the FAK/PI3K/AKT signaling pathway through ITGB4

2022

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Hepatocellular carcinoma (HCC) is a malignant tumor with a high metastatic rate. Recent studies have shown that the mitosis-associated spindle-assembly checkpoint regulatory protein spindle pole body component 25 homolog (SPC25) promotes HCC progression, although the underlying mechanism has yet to be fully elucidated. The aim of the present study was to investigate the mechanism through which SPC25 may promote HCC progression in greater detail. First, the expression of SPC25 was analyzed in publicly available databases to explore the association between SPC25 and HCC metastasis. Western blotting was subsequently performed to examine the level of SPC25 expression in different HCC cell lines. SPC25 was then silenced in HCCLM3 and Huh7 cells, and the effects of SPC25 silencing were investigated using cell proliferation, wound-healing, Transwell migration assays and an in vivo mouse model. Finally, the mechanism of SPC25 action with respect to the promotion of HCC metastasis was explored using microarray analysis and rescue experiments. The results obtained demonstrated that SPC25 is highly expressed in HCC, and this high level of expression is associated with poor prognosis and metastasis. Moreover, SPC25 silencing led to a marked inhibition of the invasion and migration of HCC cells both in vitro and in vivo. The gene-expression profiling and mechanistic experiments suggest that SPC25 preferentially influences the expression of genes associated with extracellular matrix (ECM)-integrin interactions, including integrin subunit β4 (ITGB4), an upstream element of the integrin pathway. ITGB4 upregulation partly reversed the decline in cell invasion and migration capacities that resulted from SPC25 silencing. Furthermore, deleting both SPC25 and ITGB4 caused a decrease in the phosphorylation of focal adhesion kinase (FAK), phosphoinositide 3-kinase (PI3K) and AKT, which are downstream elements of the integrin pathway. Taken together, the results of the present study demonstrated the important role of SPC25 as a prognostic indicator and as a promoter of metastasis in HCC, and the underlying mechanism of its action has been partially elucidated, suggesting that SPC25 could be used as a biomarker and as a target for therapeutic intervention in the treatment of HCC.

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Normalization of Tumor Vessels by Lenvatinib‐Based Metallo‐Nanodrugs Alleviates Hypoxia and Enhances Calreticulin‐Mediated Immune Responses in Orthotopic HCC and Organoids

Zhang

Jiang

Zheng

et al. 2023

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Immunocheckpoint inhibitors combined with Lenvatinib is the first line treatment for hepatocellular carcinoma (HCC), but their potency is hampered by the low response rate and adverse events. Herein, a targeted therapeutic strategy through the coassembly of Lenvatinib, Adriamycin, Fe3+ ion, and a natural polyphenol (metallo‐nanodrugs) is presented by coordination effect for potentiating tumor vascular normalization and systematic chemo‐immunotherapy to effectively inhibit the progression of HCC in both orthotopic model and patients‐derived organoids. In mice with orthotopic HCC, the obtained metallo‐nanodrugs efficiently increase the drug accumulation in orthotopic tumors and can respond to acidic tumor environment. The promotion of tumor vascular normalization by metallo‐nanodrugs is observed, which enhances the infiltrating T lymphocytes in tumor, and reinforces the calreticulin‐mediated antitumor immunity through alleviating hypoxia, reducing regulatory T cells, and down‐regulating PDL1 expression of tumors. The excellent therapeutic efficiency with complete remission of orthotopic tumors (3/6) and long‐term survival of mice (4/6, 42 days) are also achieved. Furthermore, the excellent therapeutic effect of metallo‐nanodrugs is also validated in 5 patient‐derived organoids, and hence can provide a marvelous systemic chemo‐immunotherapy strategy for enhancing HCC treatment.

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Lenvatinib plus EGFR inhibition for liver cancer

Cited by 9 publications

References 1 publication

New Anthranilic Acid Hydrazones as Fenamate Isosteres: Synthesis, Characterization, Molecular Docking, Dynamics & in Silico ADME, in Vitro Anti‐Inflammatory and Anticancer Activity Studies

New Anthranilic Acid Hydrazones as Fenamate Isosteres: Synthesis, Characterization, Molecular Docking, Dynamics & in Silico ADME, in Vitro Anti‐Inflammatory and Anticancer Activity Studies

SPC25 promotes hepatocellular carcinoma metastasis via activating the FAK/PI3K/AKT signaling pathway through ITGB4

Normalization of Tumor Vessels by Lenvatinib‐Based Metallo‐Nanodrugs Alleviates Hypoxia and Enhances Calreticulin‐Mediated Immune Responses in Orthotopic HCC and Organoids

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