ArticleClinical cancer research : an official journal of the American Association for Cancer Research2020
Preclinical and Dose-Finding Phase I Trial Results of Combined Treatment with a TORC1/2 Inhibitor (TAK-228) and Aurora A Kinase Inhibitor (Alisertib) in Solid Tumors.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- Computation-driven discovery of novel chromone derivatives for the treatment of triple-negative breast cancerActa pharmaceutica Sinica. B · 2026Article
- Small-molecule autophagy modulators: Mechanisms, therapeutic potential, and development challenges in pathological settings.Fundamental research · 2026Review
- Programmed cell death in triple-negative breast cancer.Cellular & molecular biology letters · 2025Review
- Dual Targeting of Aurora-A and Bcl-xL Synergistically Reshapes the Immune Microenvironment and Induces Apoptosis in Breast Cancer.Cancer science · 2025Article
- Combination therapy with alisertib enhances the anti-tumor immunity induced by a liver cancer vaccine.iScience · 2025Article
- Single-Cell Profiling and Proteomics-Based Insights Into mTORC1-Mediated Angio+TAMs Polarization in Recurrent IDH-Mutant Gliomas.CNS neuroscience & therapeutics · 2025Article
- The Role of Senescence, its Therapeutic Relevance and Clinical Implications in the Tumor Microenvironment.Theranostics · 2025Review
- Article
- Unveiling Epigenetic Vulnerabilities in Triple-Negative Breast Cancer through 3D Organoid Drug Screening.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Inhibitors of phosphoinositide 3-kinase (PI3K) and phosphoinositide 3-kinase-related protein kinase family (PIKK).Journal of enzyme inhibition and medicinal chemistry · 2023Review
- Recent Advances in Drug Discovery for Triple-Negative Breast Cancer Treatment.Molecules (Basel, Switzerland) · 2023Review
- High In Vitro and In Vivo Activity of BI-847325, a Dual MEK/Aurora Kinase Inhibitor, in Human Solid and Hematologic Cancer Models.Cancer research communications · 2023Article
- Small molecule inhibitors targeting the cancers.MedComm · 2022Review
- Current and Emerging Therapeutic Approaches for Extracranial Malignant Rhabdoid Tumors.Cancer management and research · 2022Review
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Authors and funding
21 authors at 7 institutions in 1 country.
Funding
Abstract
purposeThe purpose of this study was to evaluate the rational combination of TORC1/2 inhibitor TAK-228 and Aurora A kinase inhibitor alisertib in preclinical models of triple-negative breast cancer (TNBC) and to conduct a phase I dose escalation trial in patients with advanced solid tumors. EXPERIMENTAL
designTNBC cell lines and patient-derived xenograft (PDX) models were treated with alisertib, TAK-228, or the combination and evaluated for changes in proliferation, cell cycle, mTOR pathway modulation, and terminal cellular fate, including apoptosis and senescence. A phase I clinical trial was conducted in patients with advanced solid tumors treated with escalating doses of alisertib and TAK-228 using a 3+3 design to determine the maximum tolerated dose (MTD).
resultsThe combination of TAK-228 and alisertib resulted in decreased proliferation and cell-cycle arrest in TNBC cell lines. Treatment of TNBC PDX models resulted in significant tumor growth inhibition and increased apoptosis with the combination. In the phase I dose escalation study, 18 patients with refractory solid tumors were enrolled. The MTD was alisertib 30 mg b.i.d. days 1 to 7 of a 21-day cycle and TAK-228 2 mg daily, continuous dosing. The most common treatment-related adverse events were neutropenia, fatigue, nausea, rash, mucositis, and alopecia.
conclusionsThe addition of TAK-228 to alisertib potentiates the antitumor activity of alisertib
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