ArticleDrug design, development and therapy2020
In vitro and in vivo Anti-Tumor Effects of Pan-HER Inhibitor Varlitinib on Cholangiocarcinoma Cell Lines.
Article in Drug design, development and therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 15 citations in OpenAlex.
- Varlitinib and Paclitaxel for EGFR/HER2 Co-expressing Advanced Gastric Cancer: A Multicenter Phase Ib/II Study (K-MASTER-13).Cancer research and treatment · 2024Trial
- Augmented Global Protein Acetylation Diminishes Cell Growth and Migration of Cholangiocarcinoma Cells.International journal of molecular sciences · 2024Article
- Differential Protein Expression in Response to Varlitinib Treatment in Oral Cancer Cell Line: an In Vitro Therapeutic Approach.Applied biochemistry and biotechnology · 2024Article
- A common molecular and cellular pathway in developing Alzheimer and cancer.Biochemistry and biophysics reports · 2024Review
- Combination Therapies for Advanced Biliary Tract Cancer.Journal of clinical and translational hepatology · 2023Review
- EGFR is a potential dual molecular target for cancer and Alzheimer's disease.Frontiers in pharmacology · 2023Review
- Inhibiting EGFR/HER-2 ameliorates neuroinflammatory responses and the early stage of tau pathology through DYRK1A.Frontiers in immunology · 2022Article
- The Impact of Pre-analytical Quality Initiatives on Cholangiocarcinoma Diagnostics in Thailand.Frontiers in public health · 2022Article
- Promising Molecular Targets for the Targeted Therapy of Biliary Tract Cancers: An Overview.OncoTargets and therapy · 2021Review
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCholangiocarcinoma (CCA) is a slowly progressing but highly aggressive malignancy. Targeting the HER protein family represents a potential therapeutic strategy for CCA treatment. The pan-HER inhibitor varlitinib is being developed for the treatment of breast cancer, gastric cancer, and biliary tract cancer, which includes CCA. This study aims to evaluate the anti-tumor effect of varlitinib on CCA using both in vitro and in vivo models. MATERIALS AND
methodsHER family expression profiles and the cytotoxic activity of varlitinib were determined in CCA cell lines (KKU-214, KKU-213, KKU-156 and KKU-100) and cholangiocyte (MMNK-1). Anti-proliferation and apoptosis induction were examined in KKU-214 and KKU-100 cell lines. A combination of varlitinib with PI3K inhibitor, BKM-120, was explored for efficacy in the KKU-100 cell line. In addition, the anti-tumor activity of varlitinib on CCA and the key metabolites were evaluated in tumor tissues from CCA xenograft model.
resultsElevated expressions of EGFR and HER2 were observed in KKU-214 and KKU-100 cells and varlitinib can suppress CCA cell growth in the micromolar range. Varlitinib inhibits cell proliferation and enhances cell death via the suppression of Akt and Erk1/2 activity in the KKU-214 cell line. While KKU-100 cells showed a poor response to varlitinib, a combination of varlitinib with BKM-120 improved anti-tumor activity. Varlitinib can significantly suppress tumor growth in the CCA xenograft model after oral administration for 15 days without noticeable toxicity, and aspartate can be the key metabolite to correlate with varlitinib response.
conclusionOur study indicates that varlitinib is a promising therapeutic agent for CCA treatment via the inhibition of EGFR/HER2. The anti-tumor effect of varlitinib on CCA also showed synergism in combination with PI3K inhibition. Aspartate metabolite level was correlated with varlitinib response. Combination of varlitinib with targeted drug or cytotoxic drug was recommended.
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