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Significance of PI3K Signalling pathway in clear cell renal cell carcinoma in relation to VHL and HIF status
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.ORCID iD: 0000-0002-2391-5903
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.ORCID iD: 0000-0001-6737-7230
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.ORCID iD: 0000-0002-4121-3753
2021 (English)In: Journal of Clinical Pathology, ISSN 0021-9746, E-ISSN 1472-4146, Vol. 74, no 4, p. 216-222Article, review/survey (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2021. Vol. 74, no 4, p. 216-222
Keywords [en]
ccRCC, PTEN, PI3K, VHL/HIF, signaling pathway
National Category
Cell and Molecular Biology
Research subject
Medical Cell Biology
Identifiers
URN: urn:nbn:se:umu:diva-170709DOI: 10.1136/jclinpath-2020-206693ISI: 000631874000007PubMedID: 32467322Scopus ID: 2-s2.0-85085755245OAI: oai:DiVA.org:umu-170709DiVA, id: diva2:1430001
Funder
Cancerforskningsfonden i Norrland, AMP20- 1009Available from: 2020-05-13 Created: 2020-05-13 Last updated: 2023-09-05Bibliographically approved

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Tumkur Sitaram, RaviprakashLandström, MaréneRoos, GöranLjungberg, Börje

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