ArticleCancer research2019
EGFR and c-MET Cooperate to Enhance Resistance to PARP Inhibitors in Hepatocellular Carcinoma.
Article in Cancer research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
41 citing papers in PubMed, 67 citations in OpenAlex.
- Enhancing Veliparib PARP1 inhibitor stability against UVC degradationRSC advances · 2026Article
- Defective biological networks associated with pseudogene-derived lncRNAs in cancer drug resistance: Promising prospects for their clinical targets in cancer therapy.Genes & diseases · 2026Review
- PARP‑1 in liver diseases: Molecular mechanisms, therapeutic potential and emerging clinical applications (Review).Molecular medicine reports · 2025Review
- FGFR3-induced Y158 PARP1 phosphorylation promotes PARP inhibitor resistance via BRG1/MRE11-mediated DNA repair in breast cancer models.The Journal of clinical investigation · 2025Article
- Unlocking the potential of bispecific ADCs for targeted cancer therapy.Frontiers of medicine · 2024Review
- Acetylation-dependent regulation of core spliceosome modulates hepatocellular carcinoma cassette exons and sensitivity to PARP inhibitors.Nature communications · 2024Article
- Gasdermin C sensitizes tumor cells to PARP inhibitor therapy in cancer models.The Journal of clinical investigation · 2024Article
- c-MET and the immunological landscape of cancer: novel therapeutic strategies for enhanced anti-tumor immunity.Frontiers in immunology · 2024Review
- PARP inhibitors: enhancing efficacy through rational combinations.British journal of cancer · 2023Review
- Article
- Targeting receptor tyrosine kinases in ovarian cancer: Genomic dysregulation, clinical evaluation of inhibitors, and potential for combinatorial therapies.Molecular therapy oncolytics · 2023Review
- The benefit of co-targeting PARP-1 and c-Met on the efficacy of radiotherapy in wild type BRAF melanoma.Frontiers in medicine · 2023Article
- Proteolysis-targeting chimaeras (PROTACs) as pharmacological tools and therapeutic agents: advances and future challenges.Journal of enzyme inhibition and medicinal chemistry · 2022Review
- RasGRP1 promotes the acute inflammatory response and restricts inflammation-associated cancer cell growth.Nature communications · 2022Article
- Biomarkers beyond BRCA: promising combinatorial treatment strategies in overcoming resistance to PARP inhibitors.Journal of biomedical science · 2022Review
- Inhibition of EGFR Overcomes Acquired Lenvatinib Resistance Driven by STAT3-ABCB1 Signaling in Hepatocellular Carcinoma.Cancer research · 2022Article
- Extracellular PKCδ signals to epidermal growth factor receptor for tumor proliferation in liver cancer cells.Cancer science · 2022Article
- Inhibition of BAD-Ser99 phosphorylation synergizes with PARP inhibition to ablate PTEN-deficient endometrial carcinoma.Cell death & disease · 2022Article
- Pharmacologic Induction of BRCAness inCancers · 2022Review
- EGFR/MET promotes hepatocellular carcinoma metastasis by stabilizing tumor cells and resisting to RTKs inhibitors in circulating tumor microemboli.Cell death & disease · 2022Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 3 countries.
Funding
Abstract
PARP1 inhibitors (PARPi) are currently used in the clinic for the treatment of ovarian and breast cancers, yet their therapeutic efficacy against hepatocellular carcinoma (HCC) has been disappointing. To ensure therapeutic efficacy of PARPi against HCC, a disease often diagnosed at intermediate to advanced stages with no effective treatment options, it is critical to identify not only biomarkers to predict PARPi resistance but also rational treatments to overcome this. Here, we report that a heterodimer of EGFR and MET interacts with and phosphorylates Y907 of PARP1 in the nucleus, which contributes to PARPi resistance. Inhibition of both EGFR and MET sensitized HCC cells to PARPi, and both EGFR and MET are known to be overexpressed in HCC. This report provides an explanation for the poor efficacy of PARPi against HCC and suggests combinatorial treatment consisting of EGFR, MET, and PARP inhibitors may be an effective therapeutic strategy in HCC. SIGNIFICANCE: Regulation of PARP by the c-MET and EGFR heterodimer suggests a potentially effective combination therapy to sensitize HCC to PARPi.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.