CIC-Rearranged Sarcomas: An Intriguing Entity That May Lead the Way to the Comprehension of More Common Cancers
Capicua transcriptional repressor (CIC)-rearranged sarcoma, belonging to the undifferentiated round cells sarcoma family, is characterized by high metastatic rate and poor chemo response. CIC sarcoma represents a new entity harboring the recurrent chromosomal translocation between <i<CIC</i...
Ausführliche Beschreibung
Autor*in: |
Caterina Mancarella [verfasserIn] Marianna Carrabotta [verfasserIn] Lisa Toracchio [verfasserIn] Katia Scotlandi [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2022 |
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Übergeordnetes Werk: |
In: Cancers - MDPI AG, 2010, 14(2022), 21, p 5411 |
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Übergeordnetes Werk: |
volume:14 ; year:2022 ; number:21, p 5411 |
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DOI / URN: |
10.3390/cancers14215411 |
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Katalog-ID: |
DOAJ028725174 |
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520 | |a Capicua transcriptional repressor (CIC)-rearranged sarcoma, belonging to the undifferentiated round cells sarcoma family, is characterized by high metastatic rate and poor chemo response. CIC sarcoma represents a new entity harboring the recurrent chromosomal translocation between <i<CIC</i< and, in most of the cases, <i<DUX4</i<. CIC-DUX4 imposes a CIC-specific transcriptional signature, which drives cell transformation, proliferation, and migration. While the discovery of the fusion represented the first evidence of a role of CIC in cancer, a complete comprehension of CIC-rearranged activity is still required before providing new potential avenues for therapy. To date, a specific and effective treatment for CIC sarcoma has yet to be defined. In this review, we initially highlight the clinical features and pathogenesis of CIC-rearranged sarcomas along with current therapeutic approaches and then focus on the specific oncogenic mechanisms driven by the CIC-rearrangement. We discuss novel therapeutic options evoked by the aberrant relations of CIC-DUX4 with the IGF system, DUSP6, P300/CBP, and CCNE1. We also discuss how different mutations involving <i<CIC</i< might converge on a common upregulation of CIC-target genes across human cancers. A deeper understanding of the oncogenic mechanisms driven by the chimera CIC-DUX4 might provide novel therapeutic opportunities with a general impact in cancer. | ||
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10.3390/cancers14215411 doi (DE-627)DOAJ028725174 (DE-599)DOAJ142d1f80bc234ae4bd12b512d18c1211 DE-627 ger DE-627 rakwb eng RC254-282 Caterina Mancarella verfasserin aut CIC-Rearranged Sarcomas: An Intriguing Entity That May Lead the Way to the Comprehension of More Common Cancers 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Capicua transcriptional repressor (CIC)-rearranged sarcoma, belonging to the undifferentiated round cells sarcoma family, is characterized by high metastatic rate and poor chemo response. CIC sarcoma represents a new entity harboring the recurrent chromosomal translocation between <i<CIC</i< and, in most of the cases, <i<DUX4</i<. CIC-DUX4 imposes a CIC-specific transcriptional signature, which drives cell transformation, proliferation, and migration. While the discovery of the fusion represented the first evidence of a role of CIC in cancer, a complete comprehension of CIC-rearranged activity is still required before providing new potential avenues for therapy. To date, a specific and effective treatment for CIC sarcoma has yet to be defined. In this review, we initially highlight the clinical features and pathogenesis of CIC-rearranged sarcomas along with current therapeutic approaches and then focus on the specific oncogenic mechanisms driven by the CIC-rearrangement. We discuss novel therapeutic options evoked by the aberrant relations of CIC-DUX4 with the IGF system, DUSP6, P300/CBP, and CCNE1. We also discuss how different mutations involving <i<CIC</i< might converge on a common upregulation of CIC-target genes across human cancers. A deeper understanding of the oncogenic mechanisms driven by the chimera CIC-DUX4 might provide novel therapeutic opportunities with a general impact in cancer. CIC-rearranged sarcoma CIC-DUX4 Ewing-like sarcoma DUSP6 IGF system MAPK Neoplasms. Tumors. Oncology. Including cancer and carcinogens Marianna Carrabotta verfasserin aut Lisa Toracchio verfasserin aut Katia Scotlandi verfasserin aut In Cancers MDPI AG, 2010 14(2022), 21, p 5411 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:14 year:2022 number:21, p 5411 https://doi.org/10.3390/cancers14215411 kostenfrei https://doaj.org/article/142d1f80bc234ae4bd12b512d18c1211 kostenfrei https://www.mdpi.com/2072-6694/14/21/5411 kostenfrei https://doaj.org/toc/2072-6694 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2022 21, p 5411 |
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10.3390/cancers14215411 doi (DE-627)DOAJ028725174 (DE-599)DOAJ142d1f80bc234ae4bd12b512d18c1211 DE-627 ger DE-627 rakwb eng RC254-282 Caterina Mancarella verfasserin aut CIC-Rearranged Sarcomas: An Intriguing Entity That May Lead the Way to the Comprehension of More Common Cancers 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Capicua transcriptional repressor (CIC)-rearranged sarcoma, belonging to the undifferentiated round cells sarcoma family, is characterized by high metastatic rate and poor chemo response. CIC sarcoma represents a new entity harboring the recurrent chromosomal translocation between <i<CIC</i< and, in most of the cases, <i<DUX4</i<. CIC-DUX4 imposes a CIC-specific transcriptional signature, which drives cell transformation, proliferation, and migration. While the discovery of the fusion represented the first evidence of a role of CIC in cancer, a complete comprehension of CIC-rearranged activity is still required before providing new potential avenues for therapy. To date, a specific and effective treatment for CIC sarcoma has yet to be defined. In this review, we initially highlight the clinical features and pathogenesis of CIC-rearranged sarcomas along with current therapeutic approaches and then focus on the specific oncogenic mechanisms driven by the CIC-rearrangement. We discuss novel therapeutic options evoked by the aberrant relations of CIC-DUX4 with the IGF system, DUSP6, P300/CBP, and CCNE1. We also discuss how different mutations involving <i<CIC</i< might converge on a common upregulation of CIC-target genes across human cancers. A deeper understanding of the oncogenic mechanisms driven by the chimera CIC-DUX4 might provide novel therapeutic opportunities with a general impact in cancer. CIC-rearranged sarcoma CIC-DUX4 Ewing-like sarcoma DUSP6 IGF system MAPK Neoplasms. Tumors. Oncology. Including cancer and carcinogens Marianna Carrabotta verfasserin aut Lisa Toracchio verfasserin aut Katia Scotlandi verfasserin aut In Cancers MDPI AG, 2010 14(2022), 21, p 5411 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:14 year:2022 number:21, p 5411 https://doi.org/10.3390/cancers14215411 kostenfrei https://doaj.org/article/142d1f80bc234ae4bd12b512d18c1211 kostenfrei https://www.mdpi.com/2072-6694/14/21/5411 kostenfrei https://doaj.org/toc/2072-6694 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2022 21, p 5411 |
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10.3390/cancers14215411 doi (DE-627)DOAJ028725174 (DE-599)DOAJ142d1f80bc234ae4bd12b512d18c1211 DE-627 ger DE-627 rakwb eng RC254-282 Caterina Mancarella verfasserin aut CIC-Rearranged Sarcomas: An Intriguing Entity That May Lead the Way to the Comprehension of More Common Cancers 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Capicua transcriptional repressor (CIC)-rearranged sarcoma, belonging to the undifferentiated round cells sarcoma family, is characterized by high metastatic rate and poor chemo response. CIC sarcoma represents a new entity harboring the recurrent chromosomal translocation between <i<CIC</i< and, in most of the cases, <i<DUX4</i<. CIC-DUX4 imposes a CIC-specific transcriptional signature, which drives cell transformation, proliferation, and migration. While the discovery of the fusion represented the first evidence of a role of CIC in cancer, a complete comprehension of CIC-rearranged activity is still required before providing new potential avenues for therapy. To date, a specific and effective treatment for CIC sarcoma has yet to be defined. In this review, we initially highlight the clinical features and pathogenesis of CIC-rearranged sarcomas along with current therapeutic approaches and then focus on the specific oncogenic mechanisms driven by the CIC-rearrangement. We discuss novel therapeutic options evoked by the aberrant relations of CIC-DUX4 with the IGF system, DUSP6, P300/CBP, and CCNE1. We also discuss how different mutations involving <i<CIC</i< might converge on a common upregulation of CIC-target genes across human cancers. A deeper understanding of the oncogenic mechanisms driven by the chimera CIC-DUX4 might provide novel therapeutic opportunities with a general impact in cancer. CIC-rearranged sarcoma CIC-DUX4 Ewing-like sarcoma DUSP6 IGF system MAPK Neoplasms. Tumors. Oncology. Including cancer and carcinogens Marianna Carrabotta verfasserin aut Lisa Toracchio verfasserin aut Katia Scotlandi verfasserin aut In Cancers MDPI AG, 2010 14(2022), 21, p 5411 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:14 year:2022 number:21, p 5411 https://doi.org/10.3390/cancers14215411 kostenfrei https://doaj.org/article/142d1f80bc234ae4bd12b512d18c1211 kostenfrei https://www.mdpi.com/2072-6694/14/21/5411 kostenfrei https://doaj.org/toc/2072-6694 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2022 21, p 5411 |
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10.3390/cancers14215411 doi (DE-627)DOAJ028725174 (DE-599)DOAJ142d1f80bc234ae4bd12b512d18c1211 DE-627 ger DE-627 rakwb eng RC254-282 Caterina Mancarella verfasserin aut CIC-Rearranged Sarcomas: An Intriguing Entity That May Lead the Way to the Comprehension of More Common Cancers 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Capicua transcriptional repressor (CIC)-rearranged sarcoma, belonging to the undifferentiated round cells sarcoma family, is characterized by high metastatic rate and poor chemo response. CIC sarcoma represents a new entity harboring the recurrent chromosomal translocation between <i<CIC</i< and, in most of the cases, <i<DUX4</i<. CIC-DUX4 imposes a CIC-specific transcriptional signature, which drives cell transformation, proliferation, and migration. While the discovery of the fusion represented the first evidence of a role of CIC in cancer, a complete comprehension of CIC-rearranged activity is still required before providing new potential avenues for therapy. To date, a specific and effective treatment for CIC sarcoma has yet to be defined. In this review, we initially highlight the clinical features and pathogenesis of CIC-rearranged sarcomas along with current therapeutic approaches and then focus on the specific oncogenic mechanisms driven by the CIC-rearrangement. We discuss novel therapeutic options evoked by the aberrant relations of CIC-DUX4 with the IGF system, DUSP6, P300/CBP, and CCNE1. We also discuss how different mutations involving <i<CIC</i< might converge on a common upregulation of CIC-target genes across human cancers. A deeper understanding of the oncogenic mechanisms driven by the chimera CIC-DUX4 might provide novel therapeutic opportunities with a general impact in cancer. CIC-rearranged sarcoma CIC-DUX4 Ewing-like sarcoma DUSP6 IGF system MAPK Neoplasms. Tumors. Oncology. Including cancer and carcinogens Marianna Carrabotta verfasserin aut Lisa Toracchio verfasserin aut Katia Scotlandi verfasserin aut In Cancers MDPI AG, 2010 14(2022), 21, p 5411 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:14 year:2022 number:21, p 5411 https://doi.org/10.3390/cancers14215411 kostenfrei https://doaj.org/article/142d1f80bc234ae4bd12b512d18c1211 kostenfrei https://www.mdpi.com/2072-6694/14/21/5411 kostenfrei https://doaj.org/toc/2072-6694 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2022 21, p 5411 |
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10.3390/cancers14215411 doi (DE-627)DOAJ028725174 (DE-599)DOAJ142d1f80bc234ae4bd12b512d18c1211 DE-627 ger DE-627 rakwb eng RC254-282 Caterina Mancarella verfasserin aut CIC-Rearranged Sarcomas: An Intriguing Entity That May Lead the Way to the Comprehension of More Common Cancers 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Capicua transcriptional repressor (CIC)-rearranged sarcoma, belonging to the undifferentiated round cells sarcoma family, is characterized by high metastatic rate and poor chemo response. CIC sarcoma represents a new entity harboring the recurrent chromosomal translocation between <i<CIC</i< and, in most of the cases, <i<DUX4</i<. CIC-DUX4 imposes a CIC-specific transcriptional signature, which drives cell transformation, proliferation, and migration. While the discovery of the fusion represented the first evidence of a role of CIC in cancer, a complete comprehension of CIC-rearranged activity is still required before providing new potential avenues for therapy. To date, a specific and effective treatment for CIC sarcoma has yet to be defined. In this review, we initially highlight the clinical features and pathogenesis of CIC-rearranged sarcomas along with current therapeutic approaches and then focus on the specific oncogenic mechanisms driven by the CIC-rearrangement. We discuss novel therapeutic options evoked by the aberrant relations of CIC-DUX4 with the IGF system, DUSP6, P300/CBP, and CCNE1. We also discuss how different mutations involving <i<CIC</i< might converge on a common upregulation of CIC-target genes across human cancers. A deeper understanding of the oncogenic mechanisms driven by the chimera CIC-DUX4 might provide novel therapeutic opportunities with a general impact in cancer. CIC-rearranged sarcoma CIC-DUX4 Ewing-like sarcoma DUSP6 IGF system MAPK Neoplasms. Tumors. Oncology. Including cancer and carcinogens Marianna Carrabotta verfasserin aut Lisa Toracchio verfasserin aut Katia Scotlandi verfasserin aut In Cancers MDPI AG, 2010 14(2022), 21, p 5411 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:14 year:2022 number:21, p 5411 https://doi.org/10.3390/cancers14215411 kostenfrei https://doaj.org/article/142d1f80bc234ae4bd12b512d18c1211 kostenfrei https://www.mdpi.com/2072-6694/14/21/5411 kostenfrei https://doaj.org/toc/2072-6694 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2022 21, p 5411 |
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RC254-282 CIC-Rearranged Sarcomas: An Intriguing Entity That May Lead the Way to the Comprehension of More Common Cancers CIC-rearranged sarcoma CIC-DUX4 Ewing-like sarcoma DUSP6 IGF system MAPK |
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CIC-Rearranged Sarcomas: An Intriguing Entity That May Lead the Way to the Comprehension of More Common Cancers |
abstract |
Capicua transcriptional repressor (CIC)-rearranged sarcoma, belonging to the undifferentiated round cells sarcoma family, is characterized by high metastatic rate and poor chemo response. CIC sarcoma represents a new entity harboring the recurrent chromosomal translocation between <i<CIC</i< and, in most of the cases, <i<DUX4</i<. CIC-DUX4 imposes a CIC-specific transcriptional signature, which drives cell transformation, proliferation, and migration. While the discovery of the fusion represented the first evidence of a role of CIC in cancer, a complete comprehension of CIC-rearranged activity is still required before providing new potential avenues for therapy. To date, a specific and effective treatment for CIC sarcoma has yet to be defined. In this review, we initially highlight the clinical features and pathogenesis of CIC-rearranged sarcomas along with current therapeutic approaches and then focus on the specific oncogenic mechanisms driven by the CIC-rearrangement. We discuss novel therapeutic options evoked by the aberrant relations of CIC-DUX4 with the IGF system, DUSP6, P300/CBP, and CCNE1. We also discuss how different mutations involving <i<CIC</i< might converge on a common upregulation of CIC-target genes across human cancers. A deeper understanding of the oncogenic mechanisms driven by the chimera CIC-DUX4 might provide novel therapeutic opportunities with a general impact in cancer. |
abstractGer |
Capicua transcriptional repressor (CIC)-rearranged sarcoma, belonging to the undifferentiated round cells sarcoma family, is characterized by high metastatic rate and poor chemo response. CIC sarcoma represents a new entity harboring the recurrent chromosomal translocation between <i<CIC</i< and, in most of the cases, <i<DUX4</i<. CIC-DUX4 imposes a CIC-specific transcriptional signature, which drives cell transformation, proliferation, and migration. While the discovery of the fusion represented the first evidence of a role of CIC in cancer, a complete comprehension of CIC-rearranged activity is still required before providing new potential avenues for therapy. To date, a specific and effective treatment for CIC sarcoma has yet to be defined. In this review, we initially highlight the clinical features and pathogenesis of CIC-rearranged sarcomas along with current therapeutic approaches and then focus on the specific oncogenic mechanisms driven by the CIC-rearrangement. We discuss novel therapeutic options evoked by the aberrant relations of CIC-DUX4 with the IGF system, DUSP6, P300/CBP, and CCNE1. We also discuss how different mutations involving <i<CIC</i< might converge on a common upregulation of CIC-target genes across human cancers. A deeper understanding of the oncogenic mechanisms driven by the chimera CIC-DUX4 might provide novel therapeutic opportunities with a general impact in cancer. |
abstract_unstemmed |
Capicua transcriptional repressor (CIC)-rearranged sarcoma, belonging to the undifferentiated round cells sarcoma family, is characterized by high metastatic rate and poor chemo response. CIC sarcoma represents a new entity harboring the recurrent chromosomal translocation between <i<CIC</i< and, in most of the cases, <i<DUX4</i<. CIC-DUX4 imposes a CIC-specific transcriptional signature, which drives cell transformation, proliferation, and migration. While the discovery of the fusion represented the first evidence of a role of CIC in cancer, a complete comprehension of CIC-rearranged activity is still required before providing new potential avenues for therapy. To date, a specific and effective treatment for CIC sarcoma has yet to be defined. In this review, we initially highlight the clinical features and pathogenesis of CIC-rearranged sarcomas along with current therapeutic approaches and then focus on the specific oncogenic mechanisms driven by the CIC-rearrangement. We discuss novel therapeutic options evoked by the aberrant relations of CIC-DUX4 with the IGF system, DUSP6, P300/CBP, and CCNE1. We also discuss how different mutations involving <i<CIC</i< might converge on a common upregulation of CIC-target genes across human cancers. A deeper understanding of the oncogenic mechanisms driven by the chimera CIC-DUX4 might provide novel therapeutic opportunities with a general impact in cancer. |
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CIC sarcoma represents a new entity harboring the recurrent chromosomal translocation between <i<CIC</i< and, in most of the cases, <i<DUX4</i<. CIC-DUX4 imposes a CIC-specific transcriptional signature, which drives cell transformation, proliferation, and migration. While the discovery of the fusion represented the first evidence of a role of CIC in cancer, a complete comprehension of CIC-rearranged activity is still required before providing new potential avenues for therapy. To date, a specific and effective treatment for CIC sarcoma has yet to be defined. In this review, we initially highlight the clinical features and pathogenesis of CIC-rearranged sarcomas along with current therapeutic approaches and then focus on the specific oncogenic mechanisms driven by the CIC-rearrangement. We discuss novel therapeutic options evoked by the aberrant relations of CIC-DUX4 with the IGF system, DUSP6, P300/CBP, and CCNE1. 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7.400259 |