ArticleCancer chemotherapy and pharmacology2022
Abemaciclib is synergistic with doxorubicin in osteosarcoma pre-clinical models via inhibition of CDK4/6-Cyclin D-Rb pathway.
Article in Cancer chemotherapy and pharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 13 citations in OpenAlex.
- Biomimetic Targeted Co-Delivery System Engineered from Genomic Insights for Precision Treatment of Osteosarcoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Targeting cancer-induced skeletal damage: a holistic approach to understanding pathophysiology, mechanisms, and management solutions.American journal of cancer research · 2025Review
- Review
- Osteosarcoma Multi-Omics Landscape and Subtypes.Cancers · 2023Article
- Targeted therapy for osteosarcoma: a review.Journal of cancer research and clinical oncology · 2023Review
- Drugging Hijacked Kinase Pathways in Pediatric Oncology: Opportunities and Current Scenario.Pharmaceutics · 2023Review
- Identification of abemaciclib derivatives targeting cyclin-dependent kinase 4 and 6 using molecular dynamics, binding free energy calculation, synthesis, and pharmacological evaluation.Frontiers in pharmacology · 2023Article
- An overview of resistance to chemotherapy in osteosarcoma and future perspectives.Cancer drug resistance (Alhambra, Calif.) · 2022Review
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2 authors at 1 institution in 1 country.
Funding
Abstract
backgroundOsteosarcoma is a prevalent type of bone tumor in children and adolescents, with limited treatment and poor prognosis. Abemaciclib, an inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6), is approved for the treatment of advanced breast cancer as single agent therapy and is currently under investigation in clinical trials for the treatment of several solid tumors.
methodsThe efficacy of abemaciclib was determined using osteosarcoma cellular assays and xenograft mouse model. The combination studies were performed based on the Chou-Talalay method. Immunoblotting analysis was performed to determine the underlying mechanisms of abemaciclib in osteosarcoma cell lines.
resultsAbemaciclib potently inhibits growth, anchorage-independent colony formation and survival of a panel of osteosarcoma cell lines, with IC50 range from 90 nM to >20 μM. In addition, the combination of abemaciclib and doxorubicin is synergistic and antagonistic in abemaciclib-sensitive (IC50 <1 μM) and abemaciclib-resistant (IC50 >1 μM), respectively. Abemaciclib inhibits tumor formation and growth in a dose-dependent manner without causing significant drug toxicity in mice. The combination of abemaciclib and doxorubicin results in much greater efficacy than doxorubicin alone in inhibiting tumor growth throughout the whole treatment duration. Abemaciclib acts on osteosarcoma via suppressing CDK4/6-Cyclin D-Rb pathway.
conclusionsOur pre-clinical evidence provides a rationale of initializing clinical trial of investigating the efficacy of abemaciclib in combination with doxorubicin in osteosarcoma patients. Our work also highlights the therapeutic value of CDK4/6 inhibition in osteosarcoma with proper function of Rb.
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