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Updated: Dec 20, 2025

Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane
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Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane

Published on: February 8, 2020

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Significance of PI3K signalling pathway in clear cell renal cell carcinoma in relation to VHL and HIF status

Raviprakash Tumkur Sitaram1, Maréne Landström2, Göran Roos2

  • 1Department of Medical Biosciences, Pathology, Translational Research Center (TRC), Umeå Universitet, Umeå, Väasterbotten, Sweden raviprakash@umu.se.

Journal of Clinical Pathology
|May 30, 2020
PubMed

Insights

Clear cell renal cell carcinoma (ccRCC) treatments face challenges due to drug resistance. Understanding the interplay between VHL/HIF and PI3K/AKT pathways is key for developing effective ccRCC therapies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Renal cell carcinoma (RCC) encompasses diverse tumors with genetic alterations impacting pathogenesis and prognosis.
  • Clear cell RCC (ccRCC), the most common type, often presents asymptomatically and has a poorer prognosis, being generally refractory to conventional therapies.
  • Key genetic events in ccRCC include von Hippel-Lindau (VHL) gene loss and hypoxia-inducible factor (HIF) upregulation, driving tumor growth.

Purpose of the Study:

  • To review the current understanding of the PI3K/AKT signaling pathway in ccRCC.
  • To explore the crosstalk between the VHL/HIF and PI3K/AKT pathways in ccRCC pathogenesis.
  • To provide insights into the development of targeted therapies for ccRCC.

Main Methods:

  • Literature review of scientific articles on ccRCC, VHL/HIF, and PI3K/AKT signaling pathways.
  • Analysis of genetic alterations, signaling networks, and therapeutic strategies in ccRCC.
  • Compilation of current knowledge on pathway interactions and therapeutic resistance.

Main Results:

  • The VHL/HIF pathway is central to ccRCC, promoting growth factors and interacting with other pathways like PI3K/AKT.
  • Targeted agents developed against major signaling pathways show limitations due to acquired resistance and activation of alternative pathways.
  • The PI3K/AKT pathway plays a significant role in ccRCC progression, metastasis, angiogenesis, and survival.

Conclusions:

  • The VHL/HIF and PI3K/AKT pathways are intricately linked in ccRCC development.
  • Understanding these pathway interactions is crucial for overcoming therapeutic resistance in ccRCC.
  • Further research into these pathways may lead to novel and more effective treatment strategies for ccRCC.
Keywords:
PI3KPTENVHL/HIFccRCCsignaling pathway

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