論文 - 詳細
| RRC ID | 70157 |
|---|---|
| 著者 | Stransky LA, Vigeant SM, Huang B, West D, Denize T, Walton E, Signoretti S, Kaelin WG Jr. |
| タイトル | Sensitivity of VHL mutant kidney cancers to HIF2 inhibitors does not require an intact p53 pathway. |
| ジャーナル | Proc Natl Acad Sci U S A |
| Abstract |
SignificanceVHL tumor suppressor gene inactivation is a hallmark of clear cell renal cell carcinoma (ccRCC), the most common form of kidney cancer, and promotes tumor growth by stabilizing the hypoxia-inducible factor 2 (HIF2) transcription factor. HIF2 inhibitors appear to be helpful for some, but not all, ccRCC patients in clinical trials. Previous preclinical and clinical data suggested that only ccRCCs that can activate the p53 tumor suppressor in response to DNA damage would respond to HIF2 inhibitors. Here, we show that an intact p53 pathway is neither necessary nor sufficient for the sensitivity of ccRCCs to HIF2 inhibitors, suggesting that it would be premature to use p53 status to determine which ccRCC patients should be treated with a HIF2 inhibitor. |
| 巻・号 | 119(14) |
| ページ | e2120403119 |
| 公開日 | 2022-4-5 |
| DOI | 10.1073/pnas.2120403119 |
| PMID | 35357972 |
| PMC | PMC9168943 |
| MeSH | Basic Helix-Loop-Helix Transcription Factors* / antagonists & inhibitors Basic Helix-Loop-Helix Transcription Factors* / genetics Basic Helix-Loop-Helix Transcription Factors* / metabolism Carcinoma, Renal Cell* / drug therapy Carcinoma, Renal Cell* / genetics Carcinoma, Renal Cell* / pathology Cell Line, Tumor Female Gene Expression Regulation, Neoplastic Humans Indans* / pharmacology Indans* / therapeutic use Kidney Neoplasms* / drug therapy Kidney Neoplasms* / genetics Kidney Neoplasms* / pathology Male Sulfones* / pharmacology Sulfones* / therapeutic use Tumor Suppressor Protein p53* / genetics Tumor Suppressor Protein p53* / metabolism Von Hippel-Lindau Tumor Suppressor Protein / genetics Von Hippel-Lindau Tumor Suppressor Protein / metabolism |
| IF | 9.412 |
| リソース情報 | |
| ヒト・動物細胞 | TUHR4TKB(RCB1198) TUHR10TKB(RCB1275) TUHR14TKB(RCB1383) RCC10RGB(RCB1151) |