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Tumoral cubilin is a predictive marker for treatment of renal cancer patients with sunitinib and sorafenib
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. (Gustav Ullenhag)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. (Gunilla Enblad)ORCID iD: 0000-0002-0594-724X
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab. (Tobias Sjöblom)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology. Uppsala University, Science for Life Laboratory, SciLifeLab. (Fredrik Pontén)
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2017 (English)In: Journal of Cancer Research and Clinical Oncology, ISSN 0171-5216, E-ISSN 1432-1335, Vol. 143, no 6, p. 961-970Article in journal (Refereed) Published
Abstract [en]

Purpose Tyrosine kinase inhibitors like sunitinib and sorafenib are commonly used to treat metastatic renal cell cancer patients. Cubilin is a membrane protein expressed in the proximal renal tubule. Cubilin and megalin function together as endocytic receptors mediating uptake of many proteins. There is no established predictive marker for metastatic renal cell cancer patients and the purpose of the present study was to assess if cubilin can predict response to treatment with tyrosine kinase inhibitors.

Methods Cubilin protein expression was analyzsed in tumor tissue from a cohort of patients with metastatic renal cell cancer (n = 139) using immunohistochemistry. One hundred and thirty six of the patients were treated with sunitinib or sorafenib in the first- or second-line setting. Thirty of these were censored because of toxicity leading to the termination of treatment and the remaining (n = 106) were selected for the current study.

Results Fifty-three (50%) of the tumors expressed cubilin in the membrane. The median progression-free survival was 8 months in patients with cubilin expressing tumors and 4 months in the cubilin negative group. In addition, the overall survival was better for patients with cubilin positive tumors. We also found that the fraction of cubilin negative patients was significantly higher in the non-responding group (PFS ≤3 months) compared to responding patients (PFS >3 months).

Conclusions We show for the first time that tumoral expression of cubilin is a positive predictive marker for treatment of metastatic renal cell cancer patients with sunitinib and sorafenib.

Place, publisher, year, edition, pages
2017. Vol. 143, no 6, p. 961-970
Keywords [en]
Cubilin, Predictive marker, Renal cancer, Tissue microarray, Tyrosine kinase inhibitor
National Category
Clinical Medicine Cancer and Oncology
Identifiers
URN: urn:nbn:se:uu:diva-318129DOI: 10.1007/s00432-017-2365-yISI: 000401411200005PubMedID: 28260162OAI: oai:DiVA.org:uu-318129DiVA, id: diva2:1084175
Funder
Knut and Alice Wallenberg FoundationAvailable from: 2017-03-23 Created: 2017-03-23 Last updated: 2017-06-13Bibliographically approved

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