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mTOR Signaling in Endometrial Cancer: From a Molecular and Therapeutic Point of View

  • Gynecological Cancer (H Katabuchi and H Tashiro, Section Editors)
  • Published:
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Abstract

The mammalian target of rapamycin (mTOR) plays a key role in regulating cell proliferation, metabolism, and aging, and is activated at a high frequency in various types of cancers by alterations in receptor tyrosine kinases (RTKs), RAS, phosphatidylinositol 3-kinase (PI3K), and AKT. The RTK/RAS/PI3K/AKT/mTOR signaling pathway is broadly activated in endometrial carcinomas through mutations (and/or copy number alterations) of FGFR2 (fibroblast growth factor receptor 2), KRAS, NF1, PTEN, PIK3CA, PIK3R1, PIK3R2, and AKT1. These alterations frequently coexist with the other alterations, especially in tumors with PIK3CA mutations. Although targeting mTOR signaling is a promising therapeutic strategy, single-agent mTOR inhibition showed modest clinical response (response rate < 11 %) in phase II clinical trials of endometrial cancer. We discuss how "oncogene addiction" occurs in the RTK/RAS/PI3K/AKT/mTOR signaling by reviewing integrated genomic analyses and we also explore whether novel therapies targeting this pathway might be clinically approved for endometrial cancer treatment in the future.

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Acknowledgements

We thank Keiko Shoji, Kenbun Sone, Michihiro Tanikawa, Yuichiro Miyamoto, Tomoko Kashiyama, Reiko Kurikawa, Tetsushi Tsuruga, Katsuyuki Adachi, Kazunori Nagasaka, Yoko Matsumoto, Takahide Arimoto, and Shunsuke Nakagawa for their support and assistance. This work was financially supported by The Grant-in-aid for Scientific Research (C), Grant Number 23592437, and a research program of the Project for Development of Innovative Research on Cancer Therapeutics (P-Direct), from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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Katsutoshi Oda, Yuji Ikeda, Kei Kawana, Yutaka Osuga, and Tomoyuki Fujii declare that they have no conflicts of interest.

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Correspondence to Katsutoshi Oda.

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This article is part of the Topical Collection on Gynecological Cancer

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Oda, K., Ikeda, Y., Kawana, K. et al. mTOR Signaling in Endometrial Cancer: From a Molecular and Therapeutic Point of View. Curr Obstet Gynecol Rep 4, 1–10 (2015). https://doi.org/10.1007/s13669-014-0103-x

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