Renal Cell Carcinoma in von Hippel-Lindau Disease-From Tumor Genetics to Novel Therapeutic Strategies

Frontiers in Pediatrics
Emily Kim, Stefan Zschiedrich

Abstract

von Hippel-Lindau (VHL) disease is an autosomal dominant syndrome caused by mutations in the VHL tumor-suppressor gene, leading to the dysregulation of many hypoxia-induced genes. Affected individuals are at increased risk of developing recurrent and bilateral kidney cysts and dysplastic lesions which may progress to clear cell renal cell carcinoma (ccRCC). Following the eponymous VHL gene inactivation, ccRCCs evolve through additional genetic alterations, resulting in both intratumor and intertumor heterogeneity. Genomic studies have identified frequent mutations in genes involved in epigenetic regulation and phosphoinositide 3-kinase-AKT-mechanistic target of rapamycin (mTOR) pathway activation. Currently, local therapeutic options include nephron-sparing surgery and alternative ablative procedures. For advanced metastatic disease, systemic treatment, including inhibition of vascular endothelial growth factor pathways and mTOR pathways, as well as immunotherapy are available. Multimodal therapy, targeting multiple signaling pathways and/or enhancing the immune response, is currently being investigated. A deeper understanding of the fundamental biology of ccRCC development and progression, as well as the development of novel a...Continue Reading

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Dec 5, 2020·Continuum : Lifelong Learning in Neurology·Roy E Strowd, Scott R Plotkin
Apr 4, 2021·International Journal of Molecular Sciences·Julie Xia Zhou, Xiaogang Li
May 1, 2021·International Journal of Molecular Sciences·Cassandra Millet-BoureimaChiara Gamberi
Jun 9, 2021·Journal of Experimental & Clinical Cancer Research : CR·Revati SharmaNuzhat Ahmed
Jul 22, 2021·Biomarkers in Medicine·Annette ZimpferMatthias Maruschke
Nov 25, 2021·The New England Journal of Medicine·Eric JonaschUNKNOWN MK-6482-004 Investigators
Nov 25, 2021·The New England Journal of Medicine·Manuela Schmidinger

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Methods Mentioned

BETA
exome sequencing
biopsy
xenografts

Clinical Trials Mentioned

NCT02781506
NCT02019576
NCT02978404
NCT02293980
NCT03108066

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