期刊
CURRENT OBSTETRICS AND GYNECOLOGY REPORTS
卷 4, 期 1, 页码 1-10出版社
SPRINGER
DOI: 10.1007/s13669-014-0103-x
关键词
mTOR; PI3K; AKT; PTEN; KRAS; FGFR2; Whole exome sequencing; TCGA; Endometrial cancer; Molecular target therapy
资金
- Ministry of Education, Culture, Sports, Science and Technology of Japan [23592437]
- Grants-in-Aid for Scientific Research [26462515, 23592437] Funding Source: KAKEN
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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