Drug resistance mechanism of kinase inhibitors in the treatment of hepatocellular carcinoma

Jiang, Lei; Li, Luan; Liu, Yongzhuang; Lu, Ligong; Zhan, Meixiao; Yuan, Shengtao; Liu, Yanyan

doi:10.3389/fphar.2023.1097277

Cited by 20 publications

(8 citation statements)

References 152 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In intermediate HCC patients eligible for locoregional treatment, a phase-III trial (LEAP-012) was conducted comparing lenvatinib and pembrolizumab to placebo and TACE ( Llovet et al, 2022 ). The latest published studies shed light on the clinical value of lenvatinib in HCC and provide insight into the current options for systemic treatment ( Li et al, 2022 ; Jiang et al, 2023 ; Leowattana et al, 2023 ; Su et al, 2023 ; Xie et al, 2023 ; Yang et al, 2023 ).…”

Section: Discussionmentioning

confidence: 99%

A bibliometric study on the utilization of lenvatinib in hepatocellular carcinoma (2014–2022)

Wang,

Yu,

Zhang

et al. 2023

Front. Pharmacol.

View full text Add to dashboard Cite

Background: The REFLECT phase-III trial has demonstrated the efficacy of lenvatinib in improving the overall survival of advanced hepatocellular carcinoma (HCC) patients, comparable to sorafenib. The rapidly evolving landscape of hepatocellular carcinoma therapy presents new avenues for lenvatinib. This study aims to provide a scientometric analysis of publications and predict research hotspots in this field.Methods: Relevant publications were sourced from the Web of Science Core Collection (WoSCC) database up until November 2022. The bibliometrix tool in R was employed for scientometric analysis and visualization.Results: A total of 879 publications from 2014 to 2022 were obtained from WoSCC that met the established criteria. These studies involved 4,675 researchers from 40 countries, with an average annual growth rate of 102.5%. The highest number of publications was from Japan, followed by China, Italy, and the United States. The largest proportion of studies, 14.0% (n = 123), was contributed by FUDAN UNIV. The studies were published in 274 journals, with CANCERS (n = 53) being the top journal, followed by FRONTIERS IN ONCOLOGY (n = 51) and HEPATOLOGY RESEARCH (n = 36). The top ten journals accounted for 31.5% of the 879 studies. The most prolific authors were Kudo M (n = 51), Hiraoka A (n = 43), and Tsuji K (n = 38). A total of 1,333 keywords were analyzed, with the present research hotspots being “immune checkpoint inhibitors,” “prognosis,” and “pd-1.” Co-occurrence clustering analysis revealed the top keywords, authors, publications, and journals. Strong collaboration was identified in the field.Conclusion: This scientometric and visual analysis provides a comprehensive summary of the published articles on lenvatinib in HCC during 2014–2022, highlighting the research hotspots, knowledge domain, and frontiers. The results can provide insights into future research directions in this field.

show abstract

Section: Discussionmentioning

confidence: 99%

A bibliometric study on the utilization of lenvatinib in hepatocellular carcinoma (2014–2022)

Wang,

Yu,

Zhang

et al. 2023

Front. Pharmacol.

View full text Add to dashboard Cite

show abstract

“…Shared signaling pathways between two drugs may be potentiated: for example the PI3K/Akt/mTOR pathway in the case of sorafenib and raloxifene, or inhibition of IL-6 secretion in the case of raloxifene and loratadine, or the Ras or TAK1/MEK/ERK and AP-1 in the case of sorafenib and loratadine (32). Notably, the shared pathways described have been associated with the development of resistance to sorafenib in liver cancer (33). Thus, the major clinical problem of sorafenib resistance could be evaded using the three-drug combination here studied, improving the clinical response to sorafenib.…”

Section: Induction Of Apoptosis By Sorafenib (S) Raloxifene (R) and L...mentioning

confidence: 99%

The Combination Sorafenib-raloxifene-loratadine as a Novel Potential Therapeutic Approach Against Human Liver Cancer

Villarruel-Melquiades¹,

Hernandez-Gallegos²,

Solano-Agama³

et al. 2023

In Vivo

View full text Add to dashboard Cite

Background/Aim: Liver cancer is one of the malignancies with the highest mortality-to-incidence ratio worldwide. Therefore, novel therapeutic approaches are urgently needed. Combination therapy and drug repurposing can improve the response of the patients to therapy in several cancers. The aim of the present study was to merge these two strategies and evaluate whether the twodrug-or three-drug-combination of sorafenib, raloxifene, and loratadine improves the antineoplastic effect on human liver cancer cells in comparison to the single-drug effect. Materials and Methods: The human liver cancer cell lines HepG2 and HuH7 were studied. The effect of sorafenib, raloxifene, and loratadine on the metabolic activity was determined using the MTT assay. The inhibitory concentrations (IC 20 and IC 50 ) were calculated from these results and used in the drug-combination experiments. Apoptosis and cell survival were studied by flow cytometry and using the colony formation assay, respectively. Results: In both cell lines, sorafenib, raloxifene, and loratadine in two-drug and three-drug combinations significantly reduced metabolic activity and significantly increased the percentage of apoptotic cells compared to the single-drug effect. In addition, all the combinations significantly reduced the colony-forming capacity in the HepG2 cell line. Surprisingly, the effect of raloxifene on apoptosis was similar to that observed using the combinations. Conclusion: The triple combination sorafenib-raloxifeneloratadine may be a novel promising approach in the treatment of liver cancer patients.

show abstract

“…Unfortunately, drugs targeting HCC are mostly multi-target kinase inhibitors, such as sorafenib and lenvatinib ( 3 ). Furthermore, individual sensitivity and drug resistance greatly limit their clinical application ( 4 , 5 ). Therefore, more and more attention are paid to non-kinase target proteins, such as ASCT2, SPR ( 6 , 7 ).…”

Section: Introductionmentioning

confidence: 99%

DNAJC8: a prognostic marker and potential therapeutic target for hepatocellular carcinoma

Zhang,

Ju,

Tang

et al. 2024

Front. Immunol.

View full text Add to dashboard Cite

BackgroundHepatocellular carcinoma (HCC) is the most common type of liver cancer, accounting for ~90% of the total cases. DnaJ heat shock protein family member C8 (DNAJC8), belonging to the heat shock protein 40 (HSP40) family, is known to regulate cancer biology function. However, the role of DNAJC8 on HCC development remains unknown.MethodsThe Cancer Genome Atlas, GTEx, cBioPortal, and Human Protein Atlas were used to analyze the expression and clinical significance of DNAJC8 in HCC. Two HCC cell lines, MHCC-97H and Huh-7, were utilized to determine the biological function of DNAJC8.ResultsDNAJC8 expression was upregulated in HCC tissues and correlated with poor clinical prognosis. It was closely related to spliceosome, nucleocytoplasmic transport, and cell cycle and might be involved in the formation of tumor immunosuppressive microenvironment. Knockdown of DNAJC8 severely inhibited HCC cell proliferation and induced apoptosis.ConclusionOur study demonstrate that DNAJC8 functions as an oncogene in HCC and hence may be used as a potential therapeutic target and prognostic marker for HCC.

show abstract

Drug resistance mechanism of kinase inhibitors in the treatment of hepatocellular carcinoma

Cited by 20 publications

References 152 publications

A bibliometric study on the utilization of lenvatinib in hepatocellular carcinoma (2014–2022)

A bibliometric study on the utilization of lenvatinib in hepatocellular carcinoma (2014–2022)

The Combination Sorafenib-raloxifene-loratadine as a Novel Potential Therapeutic Approach Against Human Liver Cancer

DNAJC8: a prognostic marker and potential therapeutic target for hepatocellular carcinoma

Contact Info

Product

Resources

About