ArticleBreast cancer research and treatment2019
Synergistic anti-cancer activity of CDK4/6 inhibitor palbociclib and dual mTOR kinase inhibitor MLN0128 in pRb-expressing ER-negative breast cancer.
Article in Breast cancer research and treatment, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 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.
The trial behind it
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
43 citing papers in PubMed, 60 citations in OpenAlex.
- Molecular signatures of triple-negative breast cancer cells acquiring palbociclib resistance via continuous exposure.Oncology letters · 2026Article
- Efficacy and Mechanisms of CDK4/6 Inhibitors in Breast Cancer: Advancing Targeted Therapeutic Strategies.Oncology research · 2026Review
- Establishment of matched bladder cancer PDX and PDX-derived organoid model and evaluation of anti-tumor efficacy of abemaciclib.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Article
- MicroRNA dynamics, PTEN/PI3K/AKT signaling, and their relationship to breast cancer: prospects for pharmaceuticals and natural product application.Breast cancer research and treatment · 2025Review
- The Landscape of Potential Targeted Treatments and Chemotherapy Efficacy Biomarkers for TNBC.Breast cancer (Dove Medical Press) · 2025Review
- Bioinformatics analysis identifies dysregulation of miR-548F-3p and its hub gene in triple-negative breast cancer.Iranian journal of basic medical sciences · 2025Article
- RERE-AS1 enhances the effect of CDK4/6 inhibitor Ribociclib and suppresses malignant phenotype in breast cancer via MEK/ERK pathway.Journal of translational medicine · 2024Article
- Comparative Molecular Docking of Apigenin and Luteolin versus Conventional Ligands for TP-53, pRb, APOBEC3H, and HPV-16 E6: Potential Clinical Applications in Preventing Gynecological Malignancies.Current issues in molecular biology · 2024Article
- Molecular, Cellular, and Technical Aspects of Breast Cancer Cell Lines as a Foundational Tool in Cancer Research.Life (Basel, Switzerland) · 2023Review
- The Therapeutic Potential of CDK4/6 Inhibitors, Novel Cancer Drugs, in Kidney Diseases.International journal of molecular sciences · 2023Review
- Novel combination treatment of CDK 4/6 inhibitors with PARP inhibitors in triple negative breast cancer cells.Naunyn-Schmiedeberg's archives of pharmacology · 2023Article
- The Role of Autophagy in Breast Cancer Metastasis.Biomedicines · 2023Review
- Carrier-free nanomedicines self-assembled from palbociclib dimers and Ce6 for enhanced combined chemo-photodynamic therapy of breast cancer.RSC advances · 2023Article
- Recent advances in therapeutic strategies for triple-negative breast cancer.Journal of hematology & oncology · 2022Review
- Therapeutic potential of CDK4/6 inhibitors in renal cell carcinoma.Nature reviews. Urology · 2022Review
- Comparison of the Effectiveness and Clinical Outcome of Everolimus Followed by CDK4/6 Inhibitors with the Opposite Treatment Sequence in Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer.Cancer research and treatment · 2022Article
- mTOR inhibition by TAK-228 is effective against growth, survival and angiogenesis in preclinical retinoblastoma models.Pharmacology research & perspectives · 2022Article
- Design, synthesis, and anticancer activity of three novel palbociclib derivatives.Frontiers in oncology · 2022Article
- The Combination of the CDK4/6 Inhibitor, Palbociclib, With the Vitamin DFrontiers in endocrinology · 2022Article
- CDK4/6 inhibitors: A potential therapeutic approach for triple negative breast cancer.MedComm · 2021Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
purposePalbociclib is an approved cyclin-dependent kinase (CDK) 4/6 inhibitor for treatment of patients with ER-positive and HER2-negative breast cancers. While Retinoblastoma protein (pRb), a major substrate of CDK4/6, is a potential target in triple negative breast cancer (TNBC), the usefulness of CDK4/6 inhibitors in this cancer has not been established. This preclinical study investigated the combination effects of palbociclib and the dual mammalian target of rapamycin (mTOR) kinase inhibitor MLN0128 in estrogen receptor (ER)-negative breast cancer in vitro and in vivo.
methodsThe combined effects of two drugs on three TNBC cell lines (MB231, MB468, and CAL148) and an ER-negative and HER2-positive cell line (MB453) were investigated by MTT assay and colony formation analysis. Cell cycle measurements were examined as well as changes in expression of molecules related to G1/S transition and the mTOR pathway. Importantly, a pRb-expressing TNBC patient-derived xenograft (PDX) model was used to assess the effects of the combination in vivo.
resultsA combination of palbociclib and MLN0128 synergistically inhibited the proliferation of pRb-expressing cell lines and induced G1 cell cycle arrest. Western blot analysis revealed that CDK4/6-pRb and mTOR pathways were inhibited by these treatments. In pRb-expressing TNBC PDX, the combination treatment drastically suppressed tumor growth compared to either the control or single drug treatments. In addition, the combination treatment significantly reduced the number of Ki67-positive cells.
conclusionsWe revealed that palbociclib and MLN0128 had synergistic anti-cancer activity in both pRb + ER-negative cell lines and a TNBC PDX model. Our results indicate that such combination therapy is worthy of further investigation in a clinical setting.
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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.