ArticleGastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association2021
Apatinib exhibits synergistic effect with pyrotinib and reverses acquired pyrotinib resistance in HER2-positive gastric cancer via stem cell factor/c-kit signaling and its downstream pathways.
Article in Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 42 citations in OpenAlex.
- Inetetamab combined with S-1 and oxaliplatin as first-line treatment for human epidermal growth factor receptor 2-positive gastric cancer.World journal of gastroenterology · 2024Trial
- Pyrotinib combined with apatinib for targeting metastatic non-small cell lung cancer with HER2 alterations: a prospective, open-label, single-arm phase 2 study (PATHER2).BMC medicine · 2022Trial
- Gastric Cancer-Derived Exosomes Activate Mast Cells via the SCF/c-KIT Pathway to Drive Angiogenesis and Metastasis.Oncology research · 2026Article
- Discussion on the mechanism of HER2 resistance in esophagogastric junction and gastric cancer in the era of immunotherapy.Human vaccines & immunotherapeutics · 2025Review
- Pyrotinib promotes the antitumor effect of T-DM1 by increasing drug endocytosis in HER2-positive breast cancer.Scientific reports · 2025Article
- A literature review of recent advances in gastric cancer treatment: exploring the cross-talk between targeted therapies.Cancer cell international · 2025Review
- Pyrotinib induces cell death in HER2-positive breast cancer via triggering HSP90-dependent HER2 degradation and ROS/HSF-1-dependent oxidative DNA damage.Cell stress & chaperones · 2024Article
- Disitamab vedotin combined with apatinib in gastric cancer: A case report and review of literature.World journal of clinical oncology · 2024Article
- HER2-targeted therapies beyond breast cancer - an update.Nature reviews. Clinical oncology · 2024Review
- Article
- Investigation of Molecular Mechanisms of S-1, Docetaxel and Cisplatin in Gastric Cancer with a History of Helicobacter Pylori Infection.Molecular biotechnology · 2024Article
- Elucidating molecular mechanisms and therapeutic synergy: irreversible HER2-TKI plus T-Dxd for enhanced anti-HER2 treatment of gastric cancer.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2024Article
- Pyrotinib Combined with Vinorelbine in Patients with Previously Treated HER2-Positive Metastatic Breast Cancer: A Multicenter, Single-Arm, Prospective Study.Cancer research and treatment · 2024Article
- Pyrotinib and chrysin synergistically potentiate autophagy in HER2-positive breast cancer.Signal transduction and targeted therapy · 2023Article
- Oct4 promoted proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in colon cancer cells by activating the SCF/c-Kit signaling pathway.Cell cycle (Georgetown, Tex.) · 2023Article
- Single-cell analysis reveals the potential mechanisms of pyrotinib resistance in non-small cell lung cancer.Signal transduction and targeted therapy · 2023Article
- Circulating tumor cells dynamics during chemotherapy predict survival and response in advanced non-small-cell lung cancer patients.Therapeutic advances in medical oncology · 2023Article
- The reversal of anti-HER2 resistance in advanced HER2-positive breast cancer using apatinib: two cases reports and literature review.Translational cancer research · 2022Article
- Palladium/GF-Phos-catalyzed asymmetric carbenylative amination to access chiral pyrrolidines and piperidines.Chemical science · 2022Article
- Protein tyrosine kinase inhibitor resistance in malignant tumors: molecular mechanisms and future perspective.Signal transduction and targeted therapy · 2022Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundRecently, progress has been made in the development of targeted therapies for human epidermal growth factor receptor 2 (HER2)-positive gastric cancer (GC). However, drug resistance has severely limited the efficacy of anti-HER2 therapies. Pyrotinib is a novel pan-HER inhibitor. Although it is effective in HER2-positive GC treatment, its efficacy in combination with apatinib and associated resistance mechanisms in HER2-positive GC remains unclear.
methodsIn this study, the combination effects of pyrotinib and apatinib were examined in two pyrotinib-sensitive GC cells and xenografts. The RNA sequencing was used to determine the underlying mechanisms of acquired pyrotinib resistance. The role of imatinib and apatinib in reversing pyrotinib resistance was tested in pyrotinib-resistant cells and xenografts.
resultsHere, we reported that a combination of pyrotinib and apatinib exhibits synergistic effect in HER2-positive NCI-N87 xenografts, and showed enhanced antitumor efficacy in HER2-positive GC, both in vitro and in vivo. Moreover, up-regulation of the stem cell factor (SCF) levels, and the PI3K/AKT and MAPK pathways was associated with acquired pyrotinib resistance in HER2-positive GC. Mechanistically, we demonstrated that the activation of the SCF/c-kit signaling and its downstream PI3K/AKT and MAPK pathways mediated pyrotinib resistance by promoting cell survival and proliferation. Imatinib and apatinib augmented the sensitivity of pyrotinib-resistant cells and xenografts to pyrotinib, by blocking SCF/c-kit signaling.
conclusionThese results highlight the effectiveness of pyrotinib combined with apatinib in HER2-positive GC and acquired pyrotinib resistance, thus providing a theoretical basis for new treatment methods.
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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.