Emerging roles of Aurora-A kinase in cancer therapy resistance
Aurora kinase A (Aurora-A), a serine/threonine kinase, plays a pivotal role in various cellular processes, including mitotic entry, centrosome maturation and spindle formation. Overexpression or gene-amplification/mutation of Aurora-A kinase occurs in different types of cancer, including lung cancer...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-07-01
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| Series: | Acta Pharmaceutica Sinica B |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383523001028 |
| _version_ | 1797776655600582656 |
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| author | Dayong Zheng Jun Li Han Yan Gang Zhang Wei Li Edward Chu Ning Wei |
| author_facet | Dayong Zheng Jun Li Han Yan Gang Zhang Wei Li Edward Chu Ning Wei |
| author_sort | Dayong Zheng |
| collection | DOAJ |
| description | Aurora kinase A (Aurora-A), a serine/threonine kinase, plays a pivotal role in various cellular processes, including mitotic entry, centrosome maturation and spindle formation. Overexpression or gene-amplification/mutation of Aurora-A kinase occurs in different types of cancer, including lung cancer, colorectal cancer, and breast cancer. Alteration of Aurora-A impacts multiple cancer hallmarks, especially, immortalization, energy metabolism, immune escape and cell death resistance which are involved in cancer progression and resistance. This review highlights the most recent advances in the oncogenic roles and related multiple cancer hallmarks of Aurora-A kinase-driving cancer therapy resistance, including chemoresistance (taxanes, cisplatin, cyclophosphamide), targeted therapy resistance (osimertinib, imatinib, sorafenib, etc.), endocrine therapy resistance (tamoxifen, fulvestrant) and radioresistance. Specifically, the mechanisms of Aurora-A kinase promote acquired resistance through modulating DNA damage repair, feedback activation bypass pathways, resistance to apoptosis, necroptosis and autophagy, metastasis, and stemness. Noticeably, our review also summarizes the promising synthetic lethality strategy for Aurora-A inhibitors in RB1, ARID1A and MYC gene mutation tumors, and potential synergistic strategy for mTOR, PAK1, MDM2, MEK inhibitors or PD-L1 antibodies combined with targeting Aurora-A kinase. In addition, we discuss the design and development of the novel class of Aurora-A inhibitors in precision medicine for cancer treatment. |
| first_indexed | 2024-03-12T22:53:02Z |
| format | Article |
| id | doaj.art-695e21de14304c01b520177a1eaf0b4e |
| institution | Directory Open Access Journal |
| issn | 2211-3835 |
| language | English |
| last_indexed | 2024-03-12T22:53:02Z |
| publishDate | 2023-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj.art-695e21de14304c01b520177a1eaf0b4e2023-07-20T04:38:25ZengElsevierActa Pharmaceutica Sinica B2211-38352023-07-0113728262843Emerging roles of Aurora-A kinase in cancer therapy resistanceDayong Zheng0Jun Li1Han Yan2Gang Zhang3Wei Li4Edward Chu5Ning Wei6School of Pharmacy, North China University of Science and Technology, Tangshan 063210, ChinaBasic Medical Science College, Liaoning University of Traditional Chinese Medicine, Shenyang 110032, ChinaSchool of Pharmacy, North China University of Science and Technology, Tangshan 063210, ChinaDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USASchool of Pharmacy, North China University of Science and Technology, Tangshan 063210, ChinaDepartment of Oncology and Cancer Therapeutics Program, Montefiore Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Corresponding author.Department of Oncology and Cancer Therapeutics Program, Montefiore Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Corresponding author.Aurora kinase A (Aurora-A), a serine/threonine kinase, plays a pivotal role in various cellular processes, including mitotic entry, centrosome maturation and spindle formation. Overexpression or gene-amplification/mutation of Aurora-A kinase occurs in different types of cancer, including lung cancer, colorectal cancer, and breast cancer. Alteration of Aurora-A impacts multiple cancer hallmarks, especially, immortalization, energy metabolism, immune escape and cell death resistance which are involved in cancer progression and resistance. This review highlights the most recent advances in the oncogenic roles and related multiple cancer hallmarks of Aurora-A kinase-driving cancer therapy resistance, including chemoresistance (taxanes, cisplatin, cyclophosphamide), targeted therapy resistance (osimertinib, imatinib, sorafenib, etc.), endocrine therapy resistance (tamoxifen, fulvestrant) and radioresistance. Specifically, the mechanisms of Aurora-A kinase promote acquired resistance through modulating DNA damage repair, feedback activation bypass pathways, resistance to apoptosis, necroptosis and autophagy, metastasis, and stemness. Noticeably, our review also summarizes the promising synthetic lethality strategy for Aurora-A inhibitors in RB1, ARID1A and MYC gene mutation tumors, and potential synergistic strategy for mTOR, PAK1, MDM2, MEK inhibitors or PD-L1 antibodies combined with targeting Aurora-A kinase. In addition, we discuss the design and development of the novel class of Aurora-A inhibitors in precision medicine for cancer treatment.http://www.sciencedirect.com/science/article/pii/S2211383523001028Aurora-ATherapy resistanceChemoresistanceTargeted therapyRadioresistanceSynthetic lethality |
| spellingShingle | Dayong Zheng Jun Li Han Yan Gang Zhang Wei Li Edward Chu Ning Wei Emerging roles of Aurora-A kinase in cancer therapy resistance Acta Pharmaceutica Sinica B Aurora-A Therapy resistance Chemoresistance Targeted therapy Radioresistance Synthetic lethality |
| title | Emerging roles of Aurora-A kinase in cancer therapy resistance |
| title_full | Emerging roles of Aurora-A kinase in cancer therapy resistance |
| title_fullStr | Emerging roles of Aurora-A kinase in cancer therapy resistance |
| title_full_unstemmed | Emerging roles of Aurora-A kinase in cancer therapy resistance |
| title_short | Emerging roles of Aurora-A kinase in cancer therapy resistance |
| title_sort | emerging roles of aurora a kinase in cancer therapy resistance |
| topic | Aurora-A Therapy resistance Chemoresistance Targeted therapy Radioresistance Synthetic lethality |
| url | http://www.sciencedirect.com/science/article/pii/S2211383523001028 |
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