Unlabelled: Hepatocellular carcinoma (HCC) is a highly malignant tumor with a global prevalence. In addition to the existing clinical guidelines, the effectiveness of anlotinib and Aurora-A inhibitors in treating HCC has also been demonstrated. However, Anlotinib, as an anti-angiogenesis therapy, has shown significant benefits in clinical trials but is limited by its single-agent treatment and the development of drug resistance. Aurora-A inhibitors are currently being tested in clinical trials but have limited efficacy. Combination therapy may offer clear advantages over monotherapy in this context.
Methods: In this study, we used HCC cell lines to investigate whether the combination of the two drugs could enhance their individual strengths and mitigate their weaknesses, thereby providing greater clinical benefits both in vitro and in vivo.
Results: Our findings confirmed that the Aurora-A inhibitor alisertib and anlotinib exhibited a time-dose-dependent inhibitory effect on HCC cells. In vitro cytological experiments demonstrated that the combination of the two drugs synergistically inhibited cell proliferation, invasion, and metastasis, while promoting cell apoptosis. Furthermore, we identified the underlying molecular mechanism by which the combination of the Aurora-A inhibitor alisertib and anlotinib inhibited HCC through the inhibition of the NF-ĸB signaling pathway.
Conclusions: In summary, we have demonstrated the effectiveness of combining anlotinib with an Aurora-A inhibitor, which expands the potential applications of anlotinib in the clinical treatment of HCC in the future.
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http://dx.doi.org/10.1016/j.bbrc.2023.149247 | DOI Listing |
Cell Chem Biol
January 2025
Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, USA; Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA; Department of Chemistry, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address:
The N-Myc transcription factor, encoded by MYCN, is a mechanistically validated, yet challenging, target for neuroblastoma (NB) therapy development. In normal neuronal progenitors, N-Myc undergoes rapid degradation, while, in MYCN-amplified NB cells, Aurora kinase A (Aurora-A) binds to and stabilizes N-Myc, resulting in elevated protein levels. Here, we demonstrate that targeted protein degradation of Aurora-A decreases N-Myc levels.
View Article and Find Full Text PDFJ Immunother Cancer
January 2025
Department of Thoracic, Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Background: Human papillomavirus (HPV)-driven cancers include head and neck squamous cell carcinoma and cervical cancer and represent approximately 5% of all cancer cases worldwide. Standard-of-care chemotherapy, radiotherapy, and immune checkpoint inhibitors (ICIs) are associated with adverse effects and limited responses in patients with HPV-driven cancers. The integration of targeted therapies with ICIs may improve outcomes.
View Article and Find Full Text PDFCancers (Basel)
December 2024
Division of Hematology/Oncology, Department of Medicine, Mays Cancer Center, University of Texas Health San Antonio, San Antonio, TX 78229, USA.
: Aurora (AK) A/B are oncogenic mitotic kinases that when over-expressed are poor prognostic markers in mantle cell lymphoma (MCL). : Alisertib, an AK-A inhibitor, has anti-tumor activity in relapsed/refractory (r/r) MCL patients. We evaluated alisertib plus ibrutinib in MCL to abrogate ibrutinib resistance.
View Article and Find Full Text PDFJ Nanobiotechnology
December 2024
Department of Urology, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui, China.
Castration-resistant prostate cancer (CRPC) presents significant therapeutic challenges due to its aggressive nature and poor prognosis. Targeting Aurora-A kinase (AURKA) has shown promise in cancer treatment. This study investigates the efficacy of ART-T cell membrane-encapsulated AMS@AD (CM-AMS@AD) nanoparticles (NPs) in a photothermal-chemotherapy-immunotherapy combination for CRPC.
View Article and Find Full Text PDFFuture Med Chem
January 2025
Department of Chemistry, College of Science, Taibah University, Al-Madinah, Al-Munawarah, Saudi Arabia.
Aim: Benzimidazole-triazole conjugates are very active hotspot for design and synthesis of promising anticancer agents. The target analogs showed potent and selective cytotoxicity over different cancer cell lines for breast and lung ones.
Materials & Methods: A new series of bis-1,4-disubstituted-1,2,3-triazoles moieties conjugated with a 2-mercapto-benzimidazole 4a-h and 7a-g was synthesized via the click cycloaddition (CuAAC) reaction.
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