| Title |
HIF pathway and c-Myc as biomarkers for response to sunitinib in metastatic clear-cell renal cell carcinoma
|
|---|---|
| Published in |
OncoTargets and therapy, September 2017
|
| DOI | 10.2147/ott.s137677 |
| Pubmed ID | |
| Authors |
P Maroto, E Esteban, E Fernández Parra, MJ Mendez-Vidal, M Domenech, B Pérez-Valderrama, V Calderero, JL Pérez-Gracia, E Grande, F Algaba |
| Abstract |
Clear-cell renal cell carcinoma (ccRCC) is a heterogeneous disease with a different clinical behavior and response to targeted therapies. Differences in hypoxia-inducible factor (HIF) expression have been used to classify von Hippel-Lindau gene (VHL)-deficient ccRCC tumors. c-Myc may be driving proliferation in HIF-2α-expressing tumors in a growth factor-independent manner. To explore the HIF-1α, HIF-2α and c-Myc baseline expression as potential predictors of sunitinib outcome as well as the effectiveness and safety with sunitinib in patients with metastatic ccRCC in routine clinical practice. This was an observational and prospective study involving 10 Spanish hospitals. Formalin-fixed, paraffin-embedded primary tumor samples from metastatic ccRCC patients who received sunitinib as first-line treatment were analyzed. Association between biomarker expression and sunitinib treatment outcomes was evaluated. Kaplan-Meier method was applied to measure progression-free survival (PFS) and overall survival. Eighty-one patients were included: median PFS was 10.8 months (95% CI: 7.4-13.5 months), median overall survival was 21.8 months (95% CI: 14.7-29.8 months) and objective response rate was 40.7%, with 7.4% of patients achieving a complete response. Molecular marker staining was performed in the 69 available tumor samples. Significant association with lower PFS was identified for double c-Myc/HIF-2α-positive staining tumors (median 4.3 vs 11.5 months, hazard ratio =2.64, 95% CI: 1.03-6.80, P=0.036). A trend toward a lower PFS was found in positive c-Myc tumors (median 5.9 vs 10.9 months, P=0.263). HIF-1α and HIF-2α expression levels were not associated with clinical outcome. These preliminary results suggest that predictive subgroups might be defined based on biomarkers such as c-Myc/HIF-2α. Further validation with more patients will be needed in order to confirm it. Outcomes with sunitinib in metastatic ccRCC in daily clinical practice resemble those obtained in clinical trials. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Canada | 1 | 50% |
| Unknown | 1 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 18 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 18 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 4 | 22% |
| Student > Ph. D. Student | 4 | 22% |
| Professor | 2 | 11% |
| Student > Doctoral Student | 1 | 6% |
| Other | 1 | 6% |
| Other | 3 | 17% |
| Unknown | 3 | 17% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 7 | 39% |
| Biochemistry, Genetics and Molecular Biology | 3 | 17% |
| Agricultural and Biological Sciences | 2 | 11% |
| Psychology | 1 | 6% |
| Unknown | 5 | 28% |
Attention Score in Context
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 18 October 2017.
All research outputs
#17,032,385
of 25,806,080 outputs
Outputs from OncoTargets and therapy
#999
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Outputs of similar age
#197,942
of 325,646 outputs
Outputs of similar age from OncoTargets and therapy
#31
of 75 outputs
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