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Tumoral cubilin is a predictive marker for treatment of renal cancer patients with sunitinib and sorafenib.

ABSTRACT: 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.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.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).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.

SUBMITTER: Niinivirta M

PROVIDER: S-EPMC5427164 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Tumoral cubilin is a predictive marker for treatment of renal cancer patients with sunitinib and sorafenib.

Niinivirta Marjut M Enblad Gunilla G Edqvist Per-Henrik PH Pontén Fredrik F Dragomir Anca A Ullenhag Gustav J GJ

Journal of cancer research and clinical oncology 20170304 6

<h4>Purpose</h4>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 ki ...[more]

PMID: 28260162

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Project description:Impairment of cognitive functioning has been reported in several studies in patients treated with chemotherapy. So far, no studies have been published on the effects of the vascular endothelial growth factor receptor (VEGFR) inhibitors on cognitive functioning. We investigated the objective and subjective cognitive function of patients during treatment with VEGFR tyrosine kinase inhibitors (VEGFR TKI).Three groups of participants, matched on age, sex and education, were enrolled; 1. metastatic renal cell cancer (mRCC) or GIST patients treated with sunitinib or sorafenib (VEGFR TKI patients n = 30); 2. patients with mRCC not receiving systemic treatment (patient controls n = 20); 3. healthy controls (n = 30). Sixteen neuropsychological tests examining the main cognitive domains (intelligence, memory, attention and concentration, executive functions and abstract reasoning) were administered by a neuropsychologist. Four questionnaires were used to assess subjective cognitive complaints, mood, fatigue and psychological wellbeing.No significant differences in mean age, sex distribution, education level or IQ were found between the three groups. Both patient groups performed significantly worse on the cognitive domains Learning & Memory and Executive Functions (Response Generation and Problem Solving) compared to healthy controls. However only the VEGFR TKI patients showed impairments on the Executive subdomain Response Generation. Effect sizes of cognitive dysfunction in patients using VEGFR TKI were larger on the domains Learning & Memory and Executive Functions, compared to patient controls. Both patients groups performed on the domain Attention & Concentration the same as the healthy controls. Longer duration of treatment on VEGFR TKI was associated with a worse score on Working Memory tasks.Our data suggest that treatment with VEGFR TKI has a negative impact on cognitive functioning, specifically on Learning & Memory, and Executive Functioning. We propose that patients who are treated with VEGFR TKI are monitored and informed for possible signs or symptoms associated with cognitive impairment.ClinicalTrials.gov Identifier: NCT01246843.

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Tumoral cubilin is a predictive marker for treatment of renal cancer patients with sunitinib and sorafenib.

Publications

Tumoral cubilin is a predictive marker for treatment of renal cancer patients with sunitinib and sorafenib.

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