ArticleGastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association2021
WEE1 inhibition reverses trastuzumab resistance in HER2-positive cancers.
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 22 papers.
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Who cites it
22 citing papers in PubMed, 31 citations in OpenAlex.
- Research progress ofFrontiers in immunology · 2026Review
- Discussion on the mechanism of HER2 resistance in esophagogastric junction and gastric cancer in the era of immunotherapy.Human vaccines & immunotherapeutics · 2025Review
- YAP as a therapeutic target to reverse trastuzumab resistance.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2025Article
- Galectin-9-An Emerging Glyco-Immune Checkpoint Target for Cancer Therapy.International journal of molecular sciences · 2025Review
- High WEE1 expression is independently linked to poor survival in multiple myeloma.Blood cancer journal · 2025Article
- circUBR5 promotes ribosome biogenesis and induces docetaxel resistance in triple-negative breast cancer cell lines via the miR-340-5p/CMTM6/c-MYC axis.Neoplasia (New York, N.Y.) · 2025Article
- The influence ofFrontiers in immunology · 2025Article
- Bioinformatics Analysis of Programmed Death-1-Trastuzumab Resistance Regulatory Networks in Breast Cancer Cells.Asian Pacific journal of cancer prevention : APJCP · 2025Article
- High WEE1 expression is independently linked to poor survival in multiple myeloma.bioRxiv : the preprint server for biology · 2024Article
- HER2-targeted therapies beyond breast cancer - an update.Nature reviews. Clinical oncology · 2024Review
- Recent developments in immunotherapy for gastrointestinal tract cancers.Journal of hematology & oncology · 2024Review
- Tracking circulating PD-L1-positive cells to monitor the outcome of patients with gastric cancer receiving anti-HER2 plus anti-PD-1 therapy.Human cell · 2024Article
- Gene interaction network analysis in multiple myeloma detects complex immune dysregulation associated with shorter survival.Blood cancer journal · 2023Article
- Adavosertib Enhances Antitumor Activity of Trastuzumab Deruxtecan in HER2-Expressing Cancers.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Smoking induces WEE1 expression to promote docetaxel resistance in esophageal adenocarcinoma.Molecular therapy oncolytics · 2023Article
- New insights for gynecological cancer therapies: from molecular mechanisms and clinical evidence to future directions.Cancer metastasis reviews · 2023Review
- The mechanism and clinical application of DNA damage repair inhibitors combined with immune checkpoint inhibitors in the treatment of urologic cancer.Frontiers in cell and developmental biology · 2023Review
- Galectin-9 in cancer therapy: from immune checkpoint ligand to promising therapeutic target.Frontiers in cell and developmental biology · 2023Review
- CMTM6 as a master regulator of PD-L1.Cancer immunology, immunotherapy : CII · 2022Review
- HER2-targeted advanced metastatic gastric/gastroesophageal junction adenocarcinoma: treatment landscape and future perspectives.Biomarker research · 2022Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTo date, many efforts have been made to understand the resistance mechanism of trastuzumab in human epidermal growth factor receptor 2 (HER2)-positive breast and gastric cancer. However, there is still a huge unmet medical need for patients with trastuzumab resistance.
methodsIn our study, we generated four trastuzumab-resistant (HR) cancer cell lines from ERBB2-amplified gastric and biliary tract cancer cell lines (SNU-216, NCI-N87, SNU-2670, and SNU-2773).
resultsHere, we found higher PD-L1 expression in trastuzumab-resistant (HR) HER2-positive cancer cells than in parental cells, and blocking PD-L1 reversed the resistance to trastuzumab in HR cells. Trastuzumab upregulated PD-L1 expression via NF-κB activation in both parental and HR cells, however, led to DNA damage only in parental cells. The WEE1 inhibitor adavosertib, which downregulates PD-L1 expression, enhanced trastuzumab efficacy by blocking BRCA1-CMTM6-PD-L1 signals and the HER2-CDCP-1-SRC axis. Additionally, the levels of galectin-9, CD163, FoxP3, and CTLA-4 were diminished by blocking WEE1 in the presence of human PBMCs in vitro.
conclusionTaken together, the strategy of co-targeting HER2 and WEE1 could overcome resistance to trastuzumab in HER2-positive cancers, supporting further clinical development in HER2-positive cancer patients.
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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.