Potential biomarkers for the therapeutic efficacy of sorafenib, sunitinib and everolimus

  • Authors:
    • Yasushi Nakai
    • Makito Miyake
    • Yosuke Morizawa
    • Shunta Hori
    • Yoshihiro Tatsumi
    • Satoshi Anai
    • Sayuri Onishi
    • Nobumichi Tanaka
    • Kiyohide Fujimoto
  • View Affiliations

  • Published online on: November 8, 2016     https://doi.org/10.3892/or.2016.5232
  • Pages: 227-234
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Abstract

We examined extracellular signal‑regulated kinase (ERK), 4E‑binding protein 1 (4EBP1) and p70 ribosomal S6 kinase (p70) as potential biomarkers for pretreatment prediction of the prognosis of patients with metastatic renal cell carcinoma (RCC) treated with sorafenib, sunitinib or everolimus. 786‑O and 769‑P cells were treated with sorafenib, sunitinib and everolimus. The expression of phosphorylated/total ERK, phosphorylated/total 4EBP1 and phosphorylated/total p70 was evaluated using western blotting. ERK, 4EBP1 and p70 were knocked down by siRNA in 786‑O and 769‑P cells. Then, the viability after treatment with each drug was assessed. Expression of phosphorylated (phospho)‑ERK, -4EBP1 and -p70 was immunohistochemically evaluated in radical nephrectomy specimens and correlated with progression‑free survival during treatment with each molecular targeting agent. Sorafenib inhibited the expression of phospho-ERK and -4EBP1 in 769‑P cells; sunitinib, phospho-ERK and -4EBP1 in 786‑O and 769‑P cells; and everolimus, phospho-p70 in 786‑O and 769‑P cells. Knockdown of ERK reduced sensitivity to sorafenib in both cell lines, knockdown of ERK and 4EBP1 reduced sensitivity to sunitinib in 769‑P cells, and knockdown of 4EBP1 and p70 reduced sensitivity to everolimus in 786‑O cells. High expression of phospho-ERK, -4EBP1 and -p70 correlated with better progression‑free survival in patients treated with sorafenib, sunitinib and everolimus, respectively. Our results indicate that phospho-ERK, -4EBP1 and/or -ERK, and phospho-p70 can be used as biomarkers for the therapeutic efficacy of sorafenib, sunitinib and everolimus, respectively.
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January-2017
Volume 37 Issue 1

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Nakai Y, Miyake M, Morizawa Y, Hori S, Tatsumi Y, Anai S, Onishi S, Tanaka N and Fujimoto K: Potential biomarkers for the therapeutic efficacy of sorafenib, sunitinib and everolimus. Oncol Rep 37: 227-234, 2017
APA
Nakai, Y., Miyake, M., Morizawa, Y., Hori, S., Tatsumi, Y., Anai, S. ... Fujimoto, K. (2017). Potential biomarkers for the therapeutic efficacy of sorafenib, sunitinib and everolimus. Oncology Reports, 37, 227-234. https://doi.org/10.3892/or.2016.5232
MLA
Nakai, Y., Miyake, M., Morizawa, Y., Hori, S., Tatsumi, Y., Anai, S., Onishi, S., Tanaka, N., Fujimoto, K."Potential biomarkers for the therapeutic efficacy of sorafenib, sunitinib and everolimus". Oncology Reports 37.1 (2017): 227-234.
Chicago
Nakai, Y., Miyake, M., Morizawa, Y., Hori, S., Tatsumi, Y., Anai, S., Onishi, S., Tanaka, N., Fujimoto, K."Potential biomarkers for the therapeutic efficacy of sorafenib, sunitinib and everolimus". Oncology Reports 37, no. 1 (2017): 227-234. https://doi.org/10.3892/or.2016.5232