ArticleOncogene2023
Epigenetic reprogramming of cell cycle genes by ACK1 promotes breast cancer resistance to CDK4/6 inhibitor.
Article in Oncogene, 2023. 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, 22 citations in OpenAlex.
- Review
- Non-receptor tyrosine kinase signaling pathways and therapeutic implications.Signal transduction and targeted therapy · 2026Review
- Epigenetic regulation in cancer chemoresistance and combined therapeutic strategies.Frontiers in cell and developmental biology · 2026Review
- Targeting TNK2/ACK1 reverses the immunosuppressive tumor microenvironment and synergizes with immunochemotherapy in pancreatic cancer.Nature communications · 2025Article
- Article
- The activated tyrosine kinase ACK1 by multiple receptor tyrosine kinases promotes proliferation and invasion of mesothelioma via regulation of PI3K/AKT/mTOR and RAF/MAPK signaling pathways.Cancer gene therapy · 2025Article
- Role of the circular RNAs/microRNA/messenger RNA axis in renal cell carcinoma: From gene regulation to metabolism and immunity.iScience · 2025Review
- METTL3-modified exosomes from adipose-derived stem cells enhance the proliferation and migration of dermal fibroblasts by mediating m6A modification of CCNB1 mRNA.Archives of dermatological research · 2025Article
- Targeting CDK4/6 in breast cancer.Experimental & molecular medicine · 2025Review
- ACK1/TNK2 kinase: molecular mechanisms and emerging cancer therapeutics.Trends in pharmacological sciences · 2025Review
- Advancements in Dalpiciclib for the Treatment of Breast Cancer Patients: A Review.Breast cancer (Dove Medical Press) · 2025Review
- Understanding and overcoming CDK4/6 inhibitor resistance in HR+/HER2- metastatic breast cancer: clinical and molecular perspectives.Therapeutic advances in medical oncology · 2025Review
- Non-Receptor Tyrosine Kinases: Their Structure and Mechanistic Role in Tumor Progression and Resistance.Cancers · 2024Review
- Small molecule agents for triple negative breast cancer: Current status and future prospects.Translational oncology · 2024Review
- Prostate cancer immunotherapy: Improving clinical outcomes with a multi-pronged approach.Cell reports. Medicine · 2023Review
- Epigenomic reprogramming of therapy-resistant circulating tumor cells in colon cancer.Frontiers in cell and developmental biology · 2023Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
Hormone receptor-positive, HER2-negative advanced breast cancers exhibit high sensitivity to CDK4/6 inhibitors such as palbociclib. However, most patients inevitably develop resistance, thus identification of new actionable therapeutic targets to overcome the recurrent disease is an urgent need. Immunohistochemical studies of tissue microarray revealed increased activation of non-receptor tyrosine kinase, ACK1 (also known as TNK2) in most of the breast cancer subtypes, independent of their hormone receptor status. Chromatin immunoprecipitation studies demonstrated that the nuclear target of activated ACK1, pY88-H4 epigenetic marks, were deposited at cell cycle genes, CCNB1, CCNB2 and CDC20, which in turn initiated their efficient transcription. Pharmacological inhibition of ACK1 using its inhibitor, (R)-9b dampened CCNB1, CCNB2 and CDC20 expression, caused G2/M arrest, culminating in regression of palbociclib-resistant breast tumor growth. Further, (R)-9b suppressed expression of CXCR4 receptor, which resulted in significant impairment of metastasis of breast cancer cells to lung. Overall, our pre-clinical data identifies activated ACK1 as an oncogene that epigenetically controls the cell cycle genes governing the G2/M transition in breast cancer cells. ACK1 inhibitor, (R)-9b could be a novel therapeutic option for the breast cancer patients that have developed resistance to CDK4/6 inhibitors.
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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 Socratic graph.