ArticleJournal of experimental & clinical cancer research : CR2024
Combined inhibition of HER2 and VEGFR synergistically improves therapeutic efficacy via PI3K-AKT pathway in advanced ovarian cancer.
Article in Journal of experimental & clinical cancer research : CR, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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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
16 citing papers in PubMed, 17 citations in OpenAlex.
- Pyrimidine derivatives as anticancer agents targeting kinases: design strategies, biological evaluation, and structure-activity relationship insights.Molecular diversity · 2026Review
- Halogenated anthraquinones in breast cancer therapy: Structural modifications targeting VEGF-related angiogenesis pathways.Journal of pharmaceutical analysis · 2026Review
- DAWN trial: a prospective, multicenter, single-arm phase II study of neoadjuvant disitamab vedotin (RC48) in combination with adebrelimab, apatinib, and S-1 for locally advanced HER2-positive gastric cancer.Journal of gastrointestinal oncology · 2026Article
- MMHC-OCPR: Prediction of Platinum Response and Recurrence Risk in Ovarian Cancer with Multimodal Deep Learning.Biomedicines · 2026Article
- Biomembrane-coated Nanoparticles Targeting circHIF1α Suppress Ovarian Cancer Metastasis and Cisplatin Resistance by Mediating System Xc⁻ Inactivation via SLC7A11/SLC3A2 to Induce Ferroptosis in Cancer Stem Cells.International journal of biological sciences · 2026Article
- Case Report: Malignant transformation of deep infiltrating endometriosis: a report of two cases and literature review.Frontiers in oncology · 2026Article
- Association between HER2 expression, genomic characteristics, and tumor immune microenvironment dynamics in epithelial ovarian cancer.Frontiers in oncology · 2026Article
- Receptor Co‑targeting Strategies for Personalized Ovarian Cancer Therapy.International journal of nanomedicine · 2026Review
- Assessment of ADC Higher Order Structure Through 2D NMR Analysis.Molecules (Basel, Switzerland) · 2025Article
- Overcoming immunotherapy resistance in bladder cancer with a novel antibody-drug conjugate RC48.Journal for immunotherapy of cancer · 2025Article
- Low Antibody Dosing in Cancer Therapy: Targeted Cytotoxicity Combined with Anti-Tumour Immunostimulation.International journal of molecular sciences · 2025Review
- Epigenetic silencing of JAM3 promoted progression in serous ovarian carcinoma through PI3K/AKT pathway.Epigenomics · 2025Article
- KLC3 activates PI3K/AKT signaling and promotes ovarian cancer cell proliferation and migration through COL3A1.Oncology reports · 2025Article
- Synthesis, Antitumor Activities, and Apoptosis-Inducing Activities of Schiff's Bases Incorporating Imidazolidine-2,4-dione Scaffold: Molecular Docking Studies and Enzymatic Inhibition Activities.Pharmaceuticals (Basel, Switzerland) · 2025Article
- RNLS promotes ovarian cancer growth and inhibits ferroptosis via mediating STAT3.Frontiers in oncology · 2025Article
- Novel NO-TZDs and trimethoxychalcone-based DHPMs: design, synthesis, and biological evaluation as potential VEGFR-2 inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2024Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundOvarian cancer (OC) is a prevalent malignancy in the female reproductive system, and developing effective targeted therapies for this disease remains challenging. The aim of this study was to use clinically-relevant OC models to evaluate the therapeutic effectiveness of RC48, an antibody-drug conjugate (ADC) targeting HER2, either alone or in combination with the VEGFR inhibitor Cediranib Maleate (CM), for the treatment of advanced OC.
methodsOC tumor specimens and cell lines were analyzed to determine HER2 and VEGFR expression by Western blot, immunocytochemistry and immunofluorescence. Moreover, the OC cell lines, cell-derived xenograft (CDX) and patient-derived xenograft (PDX) models were treated with RC48 and/or CM and then subjected to cell proliferation, viability, apoptosis, and tumor growth analyses to evaluate the feasibility of combination therapy for OC both in vitro and in vivo. Additionally, RNA-Seq was performed to investigate the critical mechanism underlying the combination therapy of RC48 and CM.
resultsOur results demonstrated that RC48 alone effectively targeted and inhibited the growth of HER2-positive OC tumors in both cell lines and PDX models. Furthermore, the combination of RC48 and CM synergistically induced tumor regression in human OC cell lines, as well as CDX and PDX models. Mechanistically, we observed that the combination treatment inhibited the growth of OC cells involved inducing apoptosis and suppressing cell motility. RNA-seq analysis provided further mechanistic insights and revealed that co-administration of RC48 and CM downregulated multiple cancer-related pathways, including the AKT/mTOR pathway, cell cycle, and cell proliferation. Notably, our data further confirmed that the PI3K-AKT pathway played a key role in the inhibition of proliferation triggered by combinational treatment of RC48 and CM in OC cells.
conclusionsThese findings provide a preclinical framework supporting the potential of dual targeting HER2 and VEGFR as a promising therapeutic strategy to improve outcomes in patients with OC.
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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.