Exploratory Multi-Level Analysis of the HIF Axis in Clear-Cell Renal Cell Carcinoma and Evaluation of GN44028 as an Experimental HIF Pathway-Modulating Compound

= 185) were analysed as a complementary transcriptomic context. Nuclear, but not cytoplasmic, HIF1A and EPAS1/HIF2A expression was associated with advanced stage and shorter survival in univariable analyses. GN44028 showed the most pronounced antiproliferative effect under tested conditions and was associated with broad suppression of HIF-related transcription, whereas sunitinib was associated with increased expression of selected HIF-related genes. GN44028 did not demonstrate clear selectivity over non-malignant HK-2 cells. Overall, nuclear HIF activation is associated with aggressive ccRCC biology, and broader HIF pathway modulation warrants further experimental investigation; however, the clinical findings remain exploratory, and therapeutic selectivity and translational relevance are not yet established.

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Publication Details

Journal
International Journal of Molecular Sciences
Published
2026-04-14
DOI
https://doi.org/10.3390/ijms27083505
Primary Topic
Cancer, Hypoxia, and Metabolism
Type
article
Field-Weighted Citation Impact
0.00

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article

Exploratory Multi-Level Analysis of the HIF Axis in Clear-Cell Renal Cell Carcinoma and Evaluation of GN44028 as an Experimental HIF Pathway-Modulating Compound

Anna Kotulak‐Chrząszcz, Piotr Wierzbicki, Mateusz Czajkowski, Marzena Kogut-Wierzbicka et al.
International Journal of Molecular Sciences
Cancer, Hypoxia, and Metabolism
article

Exploratory Multi-Level Analysis of the HIF Axis in Clear-Cell Renal Cell Carcinoma and Evaluation of GN44028 as an Experimental HIF Pathway-Modulating Compound

Anna Kotulak‐Chrząszcz, Piotr Wierzbicki, Mateusz Czajkowski, Marzena Kogut-Wierzbicka, Patrik da Silva Vital, Bartłomiej E. Kraziński, Jacek Kieżun, Agnieszka Rybarczyk, Anna Olszewska, Aleksandra Kierczak, Michalina Grudzińska, Laura Wrońska, Karol Mitas, Zuzanna Rudaś
article en

Abstract

= 185) were analysed as a complementary transcriptomic context. Nuclear, but not cytoplasmic, HIF1A and EPAS1/HIF2A expression was associated with advanced stage and shorter survival in univariable analyses. GN44028 showed the most pronounced antiproliferative effect under tested conditions and was associated with broad suppression of HIF-related transcription, whereas sunitinib was associated with increased expression of selected HIF-related genes. GN44028 did not demonstrate clear selectivity over non-malignant HK-2 cells. Overall, nuclear HIF activation is associated with aggressive ccRCC biology, and broader HIF pathway modulation warrants further experimental investigation; however, the clinical findings remain exploratory, and therapeutic selectivity and translational relevance are not yet established.

International Journal of Molecular SciencesVol. 27(8)
Hospital de Câncer de Barretos (BR), State University of Applied Sciences in Elbląg (PL), University of Warmia and Mazury in Olsztyn (PL), Gdańsk Medical University (PL)
Gdański Uniwersytet Medyczny
Good health and well-being
Openalex Percentile: Top 23%
Cancer, Hypoxia, and Metabolism
DOIOpen Access PDFOpenAlex
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