Hypoxia-inducible factor (HIF) 1α and 2α levels in cell lines and human tumor predicts response to sunitinib in renal cell carcinoma (RCC)

Patel, Premal H.; Chadalavada, Rajendrakumar S.V.; Ishill, Nicole; Patil, Sheila; Reuter, Victor E.; Motzer, Robert J.; Chaganti, RS

doi:10.1200/jco.2008.26.15_suppl.5008

Cited by 43 publications

(27 citation statements)

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“…HIFa and 2a levels in cell lines and in human tumours have been shown to correlate with clinical response to sunitinib in patients with MRCC (Patel et al, 2008). Low baseline levels of sVEGFR-3 and VEGF-C have been associated with a longer TTP and an improved response rate (Rini et al, 2008b).…”

Section: Discussionmentioning

confidence: 99%

Identification of TNF-α and MMP-9 as potential baseline predictive serum markers of sunitinib activity in patients with renal cell carcinoma using a human cytokine array

et al. 2009

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BACKGROUND: Several drugs are available to treat metastatic renal-cell carcinoma (MRCC), and predictive markers to identify the most adequate treatment for each patient are needed. Our objective was to identify potential predictive markers of sunitinib activity in MRCC. METHODS: We collected sequential serum samples from 31 patients treated with sunitinib. Sera of six patients with extreme phenotypes of either marked responses or clear progressions were analysed with a Human Cytokine Array which evaluates 174 cytokines before and after treatment. Variations in cytokine signal intensity were compared between both groups and the most relevant cytokines were assessed by ELISA in all the patients. RESULTS: Twenty-seven of the 174 cytokines varied significantly between both groups. Five of them (TNF-a, MMP-9, ICAM-1, BDNF and SDF-1) were assessed by ELISA in 21 evaluable patients. TNF-a and MMP-9 baseline levels were significantly increased in nonresponders and significantly associated with reduced overall survival and time-to-progression, respectively. The area under the ROC curves for TNF-a and MMP-9 as predictive markers of sunitinib activity were 0.83 and 0.77. CONCLUSION: Baseline levels of TNF-a and MMP-9 warrant further study as predictive markers of sunitinib activity in MRCC. Selection of patients with extreme phenotypes seems a valid method to identify potential predictive factors of response.

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Section: Discussionmentioning

confidence: 99%

Identification of TNF-α and MMP-9 as potential baseline predictive serum markers of sunitinib activity in patients with renal cell carcinoma using a human cytokine array

et al. 2009

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“…12(92%) of 13 patients with high HIF-2 a expression (>50% compared to cell line control) responded to sunitinib, whereas only 4 (27%) of 15 patients with low expression of HIF-2 a showed response to sunitinib [ 74 ] . Additional study on HIF-1 a levels in those patients will be interesting to explore.…”

Section: Hif Levelsmentioning

confidence: 88%

Biomarkers for Renal Cell Carcinoma

Rathmell

2011

Kidney Cancer

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“…Biomarkers such as VHL gene mutation status [18], and HIF-1a levels in tumor tissue [19] have been investigated for their predictive ability to define patients most likely to respond to TKI's such as sunitinib, but data remain preliminary. Likewise, tumor tissue from a series of patients receiving temsirolimus has been examined for levels of phospho-S6-kinase and phosphorylated Akt, and correlated with response [20].…”

Section: Biomarkersmentioning

confidence: 99%

RAD-001: future directions

Bukowski

2009

Med Oncol

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The clinical activity of inhibitors of the mammalian target of rapamycin (mTOR) has clearly been demonstrated in patients with renal cell carcinoma. mTOR and its kinase activity is regulated by a series of upstream and downstream elements that include phosphoinositide 3-kinase (PI3K), Akt, and the tumor suppressor phosphatase and tensin homolog (PTEN). A series of preclinical and clinical findings have provided proof of principle demonstrating the relevance of this pathway in renal cell carcinoma (RCC) pathogenesis and progression. The activity of the mTOR inhibitors temsirolimus and everolimus in advanced RCC is reviewed briefly, and the future directions with this class of agents in the therapy of advanced renal cell carcinoma discussed.

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Hypoxia-inducible factor (HIF) 1α and 2α levels in cell lines and human tumor predicts response to sunitinib in renal cell carcinoma (RCC)

Cited by 43 publications

References 0 publications

Identification of TNF-α and MMP-9 as potential baseline predictive serum markers of sunitinib activity in patients with renal cell carcinoma using a human cytokine array

Identification of TNF-α and MMP-9 as potential baseline predictive serum markers of sunitinib activity in patients with renal cell carcinoma using a human cytokine array

Biomarkers for Renal Cell Carcinoma

RAD-001: future directions

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