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STAT3 polymorphism rs4796793 may be a predictive factor of tumor response to multiple tyrosine kinase inhibitors in metastatic renal cell carcinoma in Japanese population

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Abstract

Signal transducer and activator of transcription (STAT) 3 is a key factor in multiple tyrosine kinase inhibitor (mTKI)-induced growth inhibition and apoptosis of renal cell carcinoma (RCC) cells. This study aimed to identify associations between single-nucleotide polymorphisms (SNPs) in the STAT3 gene and tumor response to mTKIs in patients with metastatic RCC (mRCC). Seventy-one patients with clear cell RCC treated with any mTKI were retrospectively genotyped to elucidate a potential association between STAT3 SNPs and overall best response to drugs. Of 50 patients included for analysis, a partial or complete response was observed in 17. A significant association was found between rs4796793 alleles and tumor response [G vs. C, odds ratio (OR) 3.25, 95 % confidence interval (CI) 1.30–8.07]. There were a higher percentage of responders with the C/C genotype at rs4796793 than with the G/C + G/G genotypes (OR 4.46, 95 % CI 1.31–15.28). Time-to-event analysis demonstrated a statistically significant difference between patients with the CC genotype and those with G/C + G/G genotypes in time-to-treatment response, but not in progression-free survival or time-to-treatment failure. The rs4796793 genotype is a novel predictive factor of the response to mTKIs in patients with mRCC. However, prospective translational trials with larger patient cohorts are required to confirm these results.

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Acknowledgments

This work is supported in part by Foundation for Promotion of Cancer Research in Japan and Kurozumi Medical Foundation. The authors would like to thank Enago (www.enago.jp) for the English language review.

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Authors and Affiliations

  1. Department of Pharmacy, Kobe University Hospital, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan

    Kazuhiro Yamamoto, Takeshi Ioroi, Sachi Hirata, Tatsuya Nishioka, Manabu Kume, Hiroo Makimoto, Tsutomu Nakagawa, Takeshi Hirano & Midori Hirai

  2. Division of Pharmacokinetics, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan

    Kazuya Kanaya, Aimi Watanabe, Tsutomu Nakagawa, Takeshi Hirano & Midori Hirai

  3. Department of Clinical Psycho-Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, 1-1-1 Tsushima-naka, Okayama, 700-8530, Japan

    Kazuaki Shinomiya & Shiho Komoto

  4. Division of Urology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan

    Kenichi Harada, Hideaki Miyake & Masato Fujisawa

  5. Department of Oncology Pharmaceutical Care and Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, 1-1-1 Tsushima-naka, Okayama, 700-8530, Japan

    Manabu Suno

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  1. Kazuhiro Yamamoto
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Correspondence to Kazuhiro Yamamoto.

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Conflict of interest

H. Miyake, K. Harada, and M. Fujisawa have received lecture fees from Pfizer, while the other authors disclosed no potential conflict of interest.

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Yamamoto, K., Ioroi, T., Kanaya, K. et al. STAT3 polymorphism rs4796793 may be a predictive factor of tumor response to multiple tyrosine kinase inhibitors in metastatic renal cell carcinoma in Japanese population. Med Oncol 33, 24 (2016). https://doi.org/10.1007/s12032-016-0733-0

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