Von Hippel-Lindau tumor suppressor pathways & corresponding therapeutics in kidney cancer
| Autor: | Maxwell Shulman, Rachel Shi, Qing Zhang |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
biology
mTORC1 Synthetic lethality urologic and male genital diseases medicine.disease_cause medicine.disease Kidney Neoplasms Article Immune checkpoint Ubiquitin ligase Vascular endothelial growth factor chemistry.chemical_compound Clear cell renal cell carcinoma chemistry Von Hippel–Lindau tumor suppressor Genetics biology.protein Cancer research medicine Carcinogenesis Molecular Biology |
| Zdroj: | J Genet Genomics |
| ISSN: | 1673-8527 |
| Popis: | The identification and application of the Von Hippel-Lindau (VHL) gene is a seminal breakthrough in kidney cancer research. VHL and its protein pVHL are the root cause of most kidney cancers, and the cascading pathway below them is crucial for understanding hypoxia, in addition to the aforementioned tumorigenesis routes and treatments. We reviewed the history and functions of VHL/pVHL and Hypoxia-inducible factor (HIF), their well-known activities under low-oxygen environments as an E3 ubiquitin ligase and as a transcription factor, respectively, as well as their non-canonical functions revealed recently. Additionally, we discussed how their dysregulation promotes tumorigenesis: beginning with chromosome 3 p-arm (3p) loss/epigenetic methylation, followed by two-allele knockout, before the loss of complimentary tumor suppressor genes leads cells down predictable oncological paths. These different pathways can ultimately determine the grade, outcome, and severity of the deadliest genitourinary cancer. We finished by investigating current and proposed schemes to therapeutically treat clear cell renal cell carcinoma (ccRCC) by manipulating the hypoxic pathway utilizing Vascular Endothelial Growth Factor (VEGF) inhibitors, mammalian target of rapamycin complex 1 (mTORC1) inhibitors, small molecule HIF inhibitors, immune checkpoint blockade therapy, and synthetic lethality. |
| Databáze: | OpenAIRE |
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