Pan Aurora Kinase Inhibitor: A Promising Targeted-Therapy in Dedifferentiated Liposarcomas With Differential Efficiency Depending on Sarcoma Molecular Profile
Soft tissue sarcoma (STS) are rare and aggressive tumours. Their classification includes numerous histological subtypes of frequent poor prognosis. Liposarcomas (LPS) are the most frequent type among them, and the aggressiveness and deep localization of dedifferentiated LPS are linked to high levels...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-03-01
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| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/12/3/583 |
| _version_ | 1797716650699522048 |
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| author | Jean Camille Mattei Corinne Bouvier-Labit Doriane Barets Nicolas Macagno Mathieu Chocry Frédéric Chibon Philippe Morando Richard Alexandre Rochwerger Florence Duffaud Sylviane Olschwang Sébastien Salas Carine Jiguet-Jiglaire |
| author_facet | Jean Camille Mattei Corinne Bouvier-Labit Doriane Barets Nicolas Macagno Mathieu Chocry Frédéric Chibon Philippe Morando Richard Alexandre Rochwerger Florence Duffaud Sylviane Olschwang Sébastien Salas Carine Jiguet-Jiglaire |
| author_sort | Jean Camille Mattei |
| collection | DOAJ |
| description | Soft tissue sarcoma (STS) are rare and aggressive tumours. Their classification includes numerous histological subtypes of frequent poor prognosis. Liposarcomas (LPS) are the most frequent type among them, and the aggressiveness and deep localization of dedifferentiated LPS are linked to high levels of recurrence. Current treatments available today lead to five-year overall survival has remained stuck around 60%−70% for the past three decades. Here, we highlight a correlation between Aurora kinasa A (AURKA) and AURKB mRNA overexpression and a low metastasis - free survival. AURKA and AURKB expression analysis at genomic and protein level on a 9-STS cell lines panel highlighted STS heterogeneity, especially in LPS subtype. AURKA and AURKB inhibition by RNAi and drug targeting with AMG 900, a pan Aurora Kinase inhibitor, in four LPS cell lines reduces cell survival and clonogenic proliferation, inducing apoptosis and polyploidy. When combined with doxorubicin, the standard treatment in STS, aurora kinases inhibitor can be considered as an enhancer of standard treatment or as an independent drug. Kinome analysis suggested its effect was linked to the inhibition of the MAP-kinase pathway, with differential drug resistance profiles depending on molecular characteristics of the tumor. Aurora Kinase inhibition by AMG 900 could be a promising therapy in STS. |
| first_indexed | 2024-03-12T08:24:36Z |
| format | Article |
| id | doaj.art-6a0befdf22794f979399ea5c9bf10568 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T08:24:36Z |
| publishDate | 2020-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-6a0befdf22794f979399ea5c9bf105682023-09-02T18:11:22ZengMDPI AGCancers2072-66942020-03-0112358310.3390/cancers12030583cancers12030583Pan Aurora Kinase Inhibitor: A Promising Targeted-Therapy in Dedifferentiated Liposarcomas With Differential Efficiency Depending on Sarcoma Molecular ProfileJean Camille Mattei0Corinne Bouvier-Labit1Doriane Barets2Nicolas Macagno3Mathieu Chocry4Frédéric Chibon5Philippe Morando6Richard Alexandre Rochwerger7Florence Duffaud8Sylviane Olschwang9Sébastien Salas10Carine Jiguet-Jiglaire11Aix-Marseille University, Inserm, MMG, 13005 Marseille, FranceAix-Marseille University, Inserm, MMG, 13005 Marseille, FranceAPHM, Hôpital de la Timone, Service d’Anatomie Pathologique et de Neuropathologie, 13005 Marseille, FranceAPHM, Hôpital de la Timone, Service d’Anatomie Pathologique et de Neuropathologie, 13005 Marseille, FranceAix-Marseille University, CNRS, INP, Inst Neurophysiopathol, 13005 Marseille, FranceINSERM, UMR 1037, 31077 Toulouse, FranceAix-Marseille University, CNRS, INP, Inst Neurophysiopathol, 13005 Marseille, FranceAix-Marseille University, Inserm, MMG, 13005 Marseille, FranceAix-Marseille University, Inserm, MMG, 13005 Marseille, FranceAix-Marseille University, Inserm, MMG, 13005 Marseille, FranceAix-Marseille University, Inserm, MMG, 13005 Marseille, FranceAPHM, Hôpital de la Timone, Service d’Anatomie Pathologique et de Neuropathologie, 13005 Marseille, FranceSoft tissue sarcoma (STS) are rare and aggressive tumours. Their classification includes numerous histological subtypes of frequent poor prognosis. Liposarcomas (LPS) are the most frequent type among them, and the aggressiveness and deep localization of dedifferentiated LPS are linked to high levels of recurrence. Current treatments available today lead to five-year overall survival has remained stuck around 60%−70% for the past three decades. Here, we highlight a correlation between Aurora kinasa A (AURKA) and AURKB mRNA overexpression and a low metastasis - free survival. AURKA and AURKB expression analysis at genomic and protein level on a 9-STS cell lines panel highlighted STS heterogeneity, especially in LPS subtype. AURKA and AURKB inhibition by RNAi and drug targeting with AMG 900, a pan Aurora Kinase inhibitor, in four LPS cell lines reduces cell survival and clonogenic proliferation, inducing apoptosis and polyploidy. When combined with doxorubicin, the standard treatment in STS, aurora kinases inhibitor can be considered as an enhancer of standard treatment or as an independent drug. Kinome analysis suggested its effect was linked to the inhibition of the MAP-kinase pathway, with differential drug resistance profiles depending on molecular characteristics of the tumor. Aurora Kinase inhibition by AMG 900 could be a promising therapy in STS.https://www.mdpi.com/2072-6694/12/3/583aurora kinasesliposarcomainhibitormolecular profile |
| spellingShingle | Jean Camille Mattei Corinne Bouvier-Labit Doriane Barets Nicolas Macagno Mathieu Chocry Frédéric Chibon Philippe Morando Richard Alexandre Rochwerger Florence Duffaud Sylviane Olschwang Sébastien Salas Carine Jiguet-Jiglaire Pan Aurora Kinase Inhibitor: A Promising Targeted-Therapy in Dedifferentiated Liposarcomas With Differential Efficiency Depending on Sarcoma Molecular Profile Cancers aurora kinases liposarcoma inhibitor molecular profile |
| title | Pan Aurora Kinase Inhibitor: A Promising Targeted-Therapy in Dedifferentiated Liposarcomas With Differential Efficiency Depending on Sarcoma Molecular Profile |
| title_full | Pan Aurora Kinase Inhibitor: A Promising Targeted-Therapy in Dedifferentiated Liposarcomas With Differential Efficiency Depending on Sarcoma Molecular Profile |
| title_fullStr | Pan Aurora Kinase Inhibitor: A Promising Targeted-Therapy in Dedifferentiated Liposarcomas With Differential Efficiency Depending on Sarcoma Molecular Profile |
| title_full_unstemmed | Pan Aurora Kinase Inhibitor: A Promising Targeted-Therapy in Dedifferentiated Liposarcomas With Differential Efficiency Depending on Sarcoma Molecular Profile |
| title_short | Pan Aurora Kinase Inhibitor: A Promising Targeted-Therapy in Dedifferentiated Liposarcomas With Differential Efficiency Depending on Sarcoma Molecular Profile |
| title_sort | pan aurora kinase inhibitor a promising targeted therapy in dedifferentiated liposarcomas with differential efficiency depending on sarcoma molecular profile |
| topic | aurora kinases liposarcoma inhibitor molecular profile |
| url | https://www.mdpi.com/2072-6694/12/3/583 |
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