Therapeutic Management of Metastatic Clear Cell Renal Cell Carcinoma: A Revolution in Every Decade
Clear cell renal cell carcinoma (RCC) oncogenesis is mainly driven by <i>VHL</i> gene inactivation, leading to overexpression of vascular endothelial growth factor (VEGF). The use of tyrosine-kinase inhibitors (TKIs) directed against VEGF and its receptor (VEGFR) revolutionised the manag...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-12-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/24/6230 |
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| author | Mathieu Larroquette Félix Lefort Luc Heraudet Jean-Christophe Bernhard Alain Ravaud Charlotte Domblides Marine Gross-Goupil |
| author_facet | Mathieu Larroquette Félix Lefort Luc Heraudet Jean-Christophe Bernhard Alain Ravaud Charlotte Domblides Marine Gross-Goupil |
| author_sort | Mathieu Larroquette |
| collection | DOAJ |
| description | Clear cell renal cell carcinoma (RCC) oncogenesis is mainly driven by <i>VHL</i> gene inactivation, leading to overexpression of vascular endothelial growth factor (VEGF). The use of tyrosine-kinase inhibitors (TKIs) directed against VEGF and its receptor (VEGFR) revolutionised the management of metastatic renal cancer in the 2000s. The more recent development of next-generation TKIs such as cabozantinib or lenvatinib has made it possible to bypass some of the mechanisms of resistance to first-generation anti-VEGFR TKIs. During the decade 2010–2020, the development of immune checkpoint blockade (ICB) therapies revolutionised the management of many solid cancers, including RCC, in first- and subsequent-line settings. Dual ICB or ICB plus anti-VEGFR TKI combinations are now the standard of care for patients with advanced clear cell RCC. To optimise these combination therapies while preserving patient quality of life, escalation and de-escalation strategies are being evaluated in prospective randomised trials, based on patient selection according to their prognosis risk. Finally, new therapeutic approaches, such as targeting hypoxia-inducible factor (HIF) and the development of innovative treatments using antibody-drug conjugates (ADCs), CAR-T cells, or radiopharmaceuticals, are all potential candidates to improve further patient survival. |
| first_indexed | 2024-03-09T17:14:08Z |
| format | Article |
| id | doaj.art-30b1f907fa774e4e9918a67e0631a2fb |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T17:14:08Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-30b1f907fa774e4e9918a67e0631a2fb2023-11-24T13:48:27ZengMDPI AGCancers2072-66942022-12-011424623010.3390/cancers14246230Therapeutic Management of Metastatic Clear Cell Renal Cell Carcinoma: A Revolution in Every DecadeMathieu Larroquette0Félix Lefort1Luc Heraudet2Jean-Christophe Bernhard3Alain Ravaud4Charlotte Domblides5Marine Gross-Goupil6Department of Medical Oncology, University Hospital of Bordeaux, 33000 Bordeaux, FranceDepartment of Medical Oncology, University Hospital of Bordeaux, 33000 Bordeaux, FranceDepartment of Medical Oncology, University Hospital of Bordeaux, 33000 Bordeaux, FranceFaculty of Medicine, University of Bordeaux, 33000 Bordeaux, FranceDepartment of Medical Oncology, University Hospital of Bordeaux, 33000 Bordeaux, FranceDepartment of Medical Oncology, University Hospital of Bordeaux, 33000 Bordeaux, FranceDepartment of Medical Oncology, University Hospital of Bordeaux, 33000 Bordeaux, FranceClear cell renal cell carcinoma (RCC) oncogenesis is mainly driven by <i>VHL</i> gene inactivation, leading to overexpression of vascular endothelial growth factor (VEGF). The use of tyrosine-kinase inhibitors (TKIs) directed against VEGF and its receptor (VEGFR) revolutionised the management of metastatic renal cancer in the 2000s. The more recent development of next-generation TKIs such as cabozantinib or lenvatinib has made it possible to bypass some of the mechanisms of resistance to first-generation anti-VEGFR TKIs. During the decade 2010–2020, the development of immune checkpoint blockade (ICB) therapies revolutionised the management of many solid cancers, including RCC, in first- and subsequent-line settings. Dual ICB or ICB plus anti-VEGFR TKI combinations are now the standard of care for patients with advanced clear cell RCC. To optimise these combination therapies while preserving patient quality of life, escalation and de-escalation strategies are being evaluated in prospective randomised trials, based on patient selection according to their prognosis risk. Finally, new therapeutic approaches, such as targeting hypoxia-inducible factor (HIF) and the development of innovative treatments using antibody-drug conjugates (ADCs), CAR-T cells, or radiopharmaceuticals, are all potential candidates to improve further patient survival.https://www.mdpi.com/2072-6694/14/24/6230checkpoint inhibitorcombinationrenal cell carcinomastrategyVEGF-TKI |
| spellingShingle | Mathieu Larroquette Félix Lefort Luc Heraudet Jean-Christophe Bernhard Alain Ravaud Charlotte Domblides Marine Gross-Goupil Therapeutic Management of Metastatic Clear Cell Renal Cell Carcinoma: A Revolution in Every Decade Cancers checkpoint inhibitor combination renal cell carcinoma strategy VEGF-TKI |
| title | Therapeutic Management of Metastatic Clear Cell Renal Cell Carcinoma: A Revolution in Every Decade |
| title_full | Therapeutic Management of Metastatic Clear Cell Renal Cell Carcinoma: A Revolution in Every Decade |
| title_fullStr | Therapeutic Management of Metastatic Clear Cell Renal Cell Carcinoma: A Revolution in Every Decade |
| title_full_unstemmed | Therapeutic Management of Metastatic Clear Cell Renal Cell Carcinoma: A Revolution in Every Decade |
| title_short | Therapeutic Management of Metastatic Clear Cell Renal Cell Carcinoma: A Revolution in Every Decade |
| title_sort | therapeutic management of metastatic clear cell renal cell carcinoma a revolution in every decade |
| topic | checkpoint inhibitor combination renal cell carcinoma strategy VEGF-TKI |
| url | https://www.mdpi.com/2072-6694/14/24/6230 |
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