Kinase activity profiling in renal cell carcinoma, benign renal tissue and in response to four different tyrosine kinase inhibitors

Andliena Tahiri; Katarina Puco; Faris Naji; Vessela N. Kristensen; Glenny Cecilie Alfsen; Lorant Farkas; Frode S. Nilsen; Stig Müller; Jan Oldenburg; Jürgen Geisler

doi:10.18632/oncotarget.28257

Oncotarget

Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.

Its scope is unique. The term "oncotarget" encompasses all molecules, pathways, cellular functions, cell types, and even tissues that can be viewed as targets relevant to cancer as well as other diseases. The term was introduced in the inaugural Editorial, Introducing Oncotarget.

As of January 1, 2022, Oncotarget has shifted to a continuous publishing model. Papers will now be published continuously within yearly volumes in their final and complete form and then quickly released to Pubmed.

Subscribe to receive alerts once a paper has been published by Oncotarget.

Impact Journals, LLC is the publisher of Oncotarget: www.impactjournals.com.

Impact Journals is a member of the Wellcome Trust List of Compliant Publishers.

Impact Journals is a member of the Society for Scholarly Publishing.

On December 23, 2022, Oncotarget server experienced a DDoS attack. As a result, Oncotarget site was inaccessible for a few hours. Oncotarget team swiftly dealt with the situation and took it under control. This malicious action will be reported to the FBI.

Research Papers:

Kinase activity profiling in renal cell carcinoma, benign renal tissue and in response to four different tyrosine kinase inhibitors

Andliena Tahiri, Katarina Puco, Faris Naji, Vessela N. Kristensen, Glenny Cecilie Alfsen, Lorant Farkas, Frode S. Nilsen, Stig Müller, Jan Oldenburg and Jürgen Geisler _

PDF | Full Text | Supplementary Files | How to cite | Press Release

Oncotarget. 2022; 13:970-981. https://doi.org/10.18632/oncotarget.28257

Metrics: PDF 913 views | Full Text 2542 views | ?

Abstract

Andliena Tahiri1^,2^,3, Katarina Puco4, Faris Naji5, Vessela N. Kristensen1^,2, Glenny Cecilie Alfsen1^,6, Lorant Farkas1^,6, Frode S. Nilsen1^,7, Stig Müller1^,7^,*, Jan Oldenburg1^,4^,* and Jürgen Geisler1^,4^,*

1 Institute of Clinical Medicine, University of Oslo, Oslo, Norway

2 Department of Medical Genetics, Oslo University Hospital, Ullevål, Norway

3 Department of Clinical Molecular Biology (EpiGen), Akershus University Hospital, Lørenskog, Norway

4 Department of Oncology, Akershus University Hospital, Lørenskog, Norway

5 Pamgene International BV, ‘s-Hertogenbosch, The Netherlands

6 Department of Pathology, Akershus University Hospital, Lørenskog, Norway

7 Department of Urology, Akershus University Hospital, Lørenskog, Norway

* These authors contributed equally to this work

Correspondence to:

Jürgen Geisler,

email:

[email protected]

Keywords: kidney cancer; kinase activity; tyrosine kinase inhibitors; renal cell carcinoma; tyrosine kinase

Received: June 06, 2022 Accepted: July 01, 2022 Published: August 04, 2022

Copyright: © 2022 Tahiri et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ABSTRACT

Kinase activity is frequently altered in renal cell carcinoma (RCC), and tyrosine kinase inhibitors (TKIs) are part of the standard treatment strategy in patients with metastatic disease. However, there are still no established biomarkers to predict clinical benefits of a specific TKI. Here, we performed protein tyrosine kinase (PTK) profiling using PamChip^® technology. The aim of this study was to identify differences in PTK activity between normal and malignant kidney tissue obtained from the same patient, and to investigate the inhibitory effects of TKIs frequently used in the clinics: sunitinib, pazopanib, cabozantinib and tivozanib. Briefly, our results showed that 36 kinase substrates differs (FDR < 0.05) between normal and cancer kidney tissue, where members of the Src family kinases and the phosphoinositide-3-kinase (PI3K) pathway exhibit high activity in renal cancer. Furthermore, ex vivo treatment of clear cell RCC with TKIs revealed that pathways such as Rap1, Ras and PI3K pathways were strongly inhibited, whereas the neurotrophin pathway had increased activity upon TKI addition. In our assay, tivozanib and cabozantinib exhibited greater inhibitory effects on PTK activity compared to sunitinib and pazopanib, implying they might be better suitable as TKIs for selected RCC patients.

All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 28257

Publication Alerts

Research Papers:

Kinase activity profiling in renal cell carcinoma, benign renal tissue and in response to four different tyrosine kinase inhibitors

Abstract