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- Tumkur Sitaram, Raviprakash, 1974-, et al.
(författare)
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Role of Wnt Signaling Pathways in Clear Cell Renal Cell Carcinoma Pathogenesis in Relation to VHL and HIF Status
- 2020
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Ingår i: Clinical Oncology and Research. - 2613-4942. ; 3:3
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Forskningsöversikt (refereegranskat)abstract
- Renal cell carcinoma (RCC) encompasses various tumor types characterized by a variety of genetic abnormalities. The genetic changes, like mutations, deletions, and epigenetic alterations, can affect the signaling components and signaling networks, causing the modification of tumor pathogenesis and prognosis of RCC. The most prevalent RCC, clear cell RCC (ccRCC), is asymptomatic in the early stages, refractory to chemotherapy and radiation therapy, and has a poorer prognosis compared with the papillary and chromophobe ccRCC types. Loss of the VHL gene and upregulation of oxygen sensors, hypoxia-inducible factor alphas (HIF-α), which promote different growth factors, is a signature of sporadic ccRCC. The VHL-HIF-α and Wnt/β-catenin pathways are closely connected and contribute to the ontogeny of ccRCC. This review confines to ccRCC and the role of the Wnt/β-catenin signaling pathways and its crosstalk with VHL/HIF.
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| 2. |
- Tumkur Sitaram, Raviprakash, 1974-, et al.
(författare)
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Significance of PI3K Signalling pathway in clear cell renal cell carcinoma in relation to VHL and HIF status
- 2021
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Ingår i: Journal of Clinical Pathology. - : BMJ Publishing Group Ltd. - 0021-9746 .- 1472-4146. ; 74:4, s. 216-222
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Forskningsöversikt (refereegranskat)abstract
- Renal cell carcinoma (RCC) includes diverse tumor types characterized by various genetic abnormalities. The genetic changes, like mutations, deletions, and epigenetic alterations, play a crucial role in the modification of signaling networks, tumor pathogenesis, and prognosis. The most prevalent RCC type, clear cell RCC (ccRCC), is asymptomatic in the early stages and has a poorer prognosis compared with the papillary and the chromophobe typesRCCs. Generally, ccRCC is refractory to chemotherapy and radiation therapy. Loss of VHL gene and upregulation of hypoxia-inducible factors (HIF), the signature of most sporadic ccRCC, promote multiple growth factors. Hence, VHL/HIF and a variety of pathways, including PTEN/PI3K/AKT, are closely connected and contribute to the ontogeny of ccRCC. In the recent decade, multiple targeting agents have been developed based on blocking major signaling pathways directly or indirectly involved in ccRCC tumor progression, metastasis, angiogenesis, and survival. However, most of these drugs have limitations; either metastatic ccRCC develops resistance to these agents, or despite blocking receptors, tumor cells utilize alternate signaling pathways. This review compiles the state of knowledge about the PI3K/AKT signaling pathway confined to ccRCC and their cross-talks with VHL/HIF pathways.
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