Belzutifan, HIF-2α Inhibitor, and Clear Cell Renal Cell Carcinoma With Somatic Von-Hippel-Lindau Loss-of-Function Mutation
The Von-Hippel-Lindau (VHL) gene, acting as a tumor suppressor, plays a crucial role in the tumorigenesis of clear cell renal cell carcinoma (ccRCC). Approximately 90% of individuals with advanced ccRCC exhibit somatic mutations in the VHL gene. Belzutifan, orally administered small-molecule inhibit...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2024-02-01
|
| Series: | Journal of Investigative Medicine High Impact Case Reports |
| Online Access: | https://doi.org/10.1177/23247096241231641 |
| _version_ | 1797316051714703360 |
|---|---|
| author | Kok Hoe Chan MD Ningjing Li MD Ran Lador MD Mark Amsbaugh MD Anneliese Gonzalez MD Putao Cen MD |
| author_facet | Kok Hoe Chan MD Ningjing Li MD Ran Lador MD Mark Amsbaugh MD Anneliese Gonzalez MD Putao Cen MD |
| author_sort | Kok Hoe Chan MD |
| collection | DOAJ |
| description | The Von-Hippel-Lindau (VHL) gene, acting as a tumor suppressor, plays a crucial role in the tumorigenesis of clear cell renal cell carcinoma (ccRCC). Approximately 90% of individuals with advanced ccRCC exhibit somatic mutations in the VHL gene. Belzutifan, orally administered small-molecule inhibitor of hypoxia-induced factor-2α, has demonstrated promising efficacy in solid tumors associated with germline loss-of-function mutations in VHL, including ccRCC. However, its impact on cases with somatic or sporadic VHL mutations remains unclear. Here, we present 2 cases where belzutifan monotherapy was employed in patients with advanced ccRCC and somatic loss-of-function mutations in VHL. Both patients exhibited a swift and sustained response, underscoring the potential role of belzutifan as a viable option in second or subsequent lines of therapy for individuals with somatic VHL mutations. Despite both patients experiencing a pulmonary crisis with respiratory compromise, their rapid response to belzutifan further emphasizes its potential utility in cases involving pulmonary or visceral crises. This report contributes valuable insights into the treatment landscape for advanced ccRCC with somatic VHL mutations. |
| first_indexed | 2024-03-08T03:12:41Z |
| format | Article |
| id | doaj.art-5ab00b223f05458295a940b4481ecf77 |
| institution | Directory Open Access Journal |
| issn | 2324-7096 |
| language | English |
| last_indexed | 2024-03-08T03:12:41Z |
| publishDate | 2024-02-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Journal of Investigative Medicine High Impact Case Reports |
| spelling | doaj.art-5ab00b223f05458295a940b4481ecf772024-02-13T02:03:35ZengSAGE PublishingJournal of Investigative Medicine High Impact Case Reports2324-70962024-02-011210.1177/23247096241231641Belzutifan, HIF-2α Inhibitor, and Clear Cell Renal Cell Carcinoma With Somatic Von-Hippel-Lindau Loss-of-Function MutationKok Hoe Chan MD0Ningjing Li MD1Ran Lador MD2Mark Amsbaugh MD3Anneliese Gonzalez MD4Putao Cen MD5The University of Texas Health Science Center at Houston, USAThe University of Texas Health Science Center at Houston, USAThe University of Texas Health Science Center at Houston, USAThe University of Texas Health Science Center at Houston, USAThe University of Texas Health Science Center at Houston, USAThe University of Texas Health Science Center at Houston, USAThe Von-Hippel-Lindau (VHL) gene, acting as a tumor suppressor, plays a crucial role in the tumorigenesis of clear cell renal cell carcinoma (ccRCC). Approximately 90% of individuals with advanced ccRCC exhibit somatic mutations in the VHL gene. Belzutifan, orally administered small-molecule inhibitor of hypoxia-induced factor-2α, has demonstrated promising efficacy in solid tumors associated with germline loss-of-function mutations in VHL, including ccRCC. However, its impact on cases with somatic or sporadic VHL mutations remains unclear. Here, we present 2 cases where belzutifan monotherapy was employed in patients with advanced ccRCC and somatic loss-of-function mutations in VHL. Both patients exhibited a swift and sustained response, underscoring the potential role of belzutifan as a viable option in second or subsequent lines of therapy for individuals with somatic VHL mutations. Despite both patients experiencing a pulmonary crisis with respiratory compromise, their rapid response to belzutifan further emphasizes its potential utility in cases involving pulmonary or visceral crises. This report contributes valuable insights into the treatment landscape for advanced ccRCC with somatic VHL mutations.https://doi.org/10.1177/23247096241231641 |
| spellingShingle | Kok Hoe Chan MD Ningjing Li MD Ran Lador MD Mark Amsbaugh MD Anneliese Gonzalez MD Putao Cen MD Belzutifan, HIF-2α Inhibitor, and Clear Cell Renal Cell Carcinoma With Somatic Von-Hippel-Lindau Loss-of-Function Mutation Journal of Investigative Medicine High Impact Case Reports |
| title | Belzutifan, HIF-2α Inhibitor, and Clear Cell Renal Cell Carcinoma With Somatic Von-Hippel-Lindau Loss-of-Function Mutation |
| title_full | Belzutifan, HIF-2α Inhibitor, and Clear Cell Renal Cell Carcinoma With Somatic Von-Hippel-Lindau Loss-of-Function Mutation |
| title_fullStr | Belzutifan, HIF-2α Inhibitor, and Clear Cell Renal Cell Carcinoma With Somatic Von-Hippel-Lindau Loss-of-Function Mutation |
| title_full_unstemmed | Belzutifan, HIF-2α Inhibitor, and Clear Cell Renal Cell Carcinoma With Somatic Von-Hippel-Lindau Loss-of-Function Mutation |
| title_short | Belzutifan, HIF-2α Inhibitor, and Clear Cell Renal Cell Carcinoma With Somatic Von-Hippel-Lindau Loss-of-Function Mutation |
| title_sort | belzutifan hif 2α inhibitor and clear cell renal cell carcinoma with somatic von hippel lindau loss of function mutation |
| url | https://doi.org/10.1177/23247096241231641 |
| work_keys_str_mv | AT kokhoechanmd belzutifanhif2ainhibitorandclearcellrenalcellcarcinomawithsomaticvonhippellindaulossoffunctionmutation AT ningjinglimd belzutifanhif2ainhibitorandclearcellrenalcellcarcinomawithsomaticvonhippellindaulossoffunctionmutation AT ranladormd belzutifanhif2ainhibitorandclearcellrenalcellcarcinomawithsomaticvonhippellindaulossoffunctionmutation AT markamsbaughmd belzutifanhif2ainhibitorandclearcellrenalcellcarcinomawithsomaticvonhippellindaulossoffunctionmutation AT anneliesegonzalezmd belzutifanhif2ainhibitorandclearcellrenalcellcarcinomawithsomaticvonhippellindaulossoffunctionmutation AT putaocenmd belzutifanhif2ainhibitorandclearcellrenalcellcarcinomawithsomaticvonhippellindaulossoffunctionmutation |