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Validation of p27KIP1 expression levels as a candidate predictive biomarker of response to rapalogs in patient-derived breast tumor xenografts

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Tumor Biology

Abstract

Blockade of mammalian target of rapamycin (mTOR) is a promising area in breast cancer therapy. However, in clinical trials, objective response rate with mTOR inhibitor monotherapy in breast cancer was modest. Biomarker studies designed to identify the responders of rapalogs are of increasing interest. We validated p27KIP1 expression levels as a candidate predictive biomarker of response to rapalogs. We also analyzed the correlation between rapamycin activity and p27KIP1 expression in the primary breast cancer cells and the patient-derived breast tumor xenograft models. The cells isolated from the breast tumor tissues expressing high levels of p27KIP1 were sensitive to rapamycin, whereas the cells from the tissues expressing low levels of p27KIP1 exhibited resistance to rapamycin. The correlation between p27KIP1 expression and rapamycin antitumor activity was also observed in the patient-derived breast tumor xenograft models. Moreover, we also found rapamycin significantly decreased phosphorylated p70S6K1 and phosphorylated 4EBP1 in both samples. It seemed that the different sensitivity of tumor cells to rapamycin did not owe to its different potency against mTOR activity. We further propose p27KIP1 expression level may be also a candidate predictive biomarker of rapalogs for breast cancer therapy, which requires additional clinical validation.

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Acknowledgments

This work was supported by Zhejiang Provincial Natural Science Foundation of China (no. LY12H31001, Y2110474), National Natural Science Foundation of China (no. 81201530), and Foundation of Zhejiang Educational Committee (no. Y201121896).

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None.

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    Authors and Affiliations

    1. School of Medicine, Taizhou University, Taizhou, Zhejiang, 318000, China

      Xiao-Fei Ding & Jun Zhou

    2. Taizhou Municipal Hospital, Taizhou, Zhejiang, 318000, China

      Dong-Qing Yin & Hua-Yuan Zhang

    3. Taizhou Hospital, Taizhou, Zhejiang, 317000, China

      Qian Chen

    4. Institute of Tumor, Taizhou University, 1139 Shi-Fu Avenue, Taizhou, Zhejiang, 318000, China

      Jun Zhou & Guang Chen

    5. School of Pharmaceutical and Chemical Engineering, Taizhou University, Taizhou, Zhejiang, 318000, China

      Guang Chen

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    1. Xiao-Fei Ding
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    2. Dong-Qing Yin
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    3. Qian Chen
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    4. Hua-Yuan Zhang
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    5. Jun Zhou
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    6. Guang Chen
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    Corresponding authors

    Correspondence to Jun Zhou or Guang Chen.

    Additional information

    Xiao-Fei Ding and Dong-Qing Yin contributed equally to this work.

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    Ding, XF., Yin, DQ., Chen, Q. et al. Validation of p27KIP1 expression levels as a candidate predictive biomarker of response to rapalogs in patient-derived breast tumor xenografts. Tumor Biol. 36, 1463–1469 (2015). https://doi.org/10.1007/s13277-014-2580-y

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    • DOI: https://doi.org/10.1007/s13277-014-2580-y

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