PI3K/AKT/mTOR pathway is activated after imatinib secondary resistance in gastrointestinal stromal tumors (GISTs).

Abstract

Phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of the rapamycin (mTOR) pathway activation may be related to imatinib resistance; however, no study has focused on whether signal conduction of this pathway will change after imatinib resistance. A total of 111 GIST samples from 91 patients were used in this study, including 20 pairs of samples before and after imatinib treatment. Immunohistochemistry was performed on tissue for p-KIT (phospho-KIT), PTEN (phosphatase and tensin homolog deleted on chromosome ten), PI3K, phospho-AKT (p-AKT), phospho-4EBP1 (p-4EBP1) and phospho-S6 (p-S6RP). The activation of AKT/mTOR was significantly higher in imatinib secondary resistant GIST (53.1 %) than in imatinib-sensitive (27.1 %) and primary resistant GIST (33.3 %) (P = 0.049). In the analysis of 20 pairs of samples, comparing pre-imatinib GIST with on-treatment ones, the PI3K status was changed from inactivated to activated in four cases each in eight patients with effective imatinib and 12 patients whose secondary resistance happened, respectively. AKT/mTOR status was inactivated in pre-imatinib and on-treatment samples in eight patients with effective imatinib; however, the status of six patients was changed from inactivated to activated in 12 patients at the time of tumor progression. The negative expression of p-KIT was accompanied with PI3K pathway and/or AKT/mTOR pathway activity in some GISTs with secondary resistance. PI3K/AKT/mTOR pathway can be partly activated after imatinib secondary resistance in GIST. In this pathway, activation of AKT/mTOR is a more crucial factor, and PI3K activation may be the early part of secondary resistance.

DOI: 10.1007/s12032-015-0554-6
050100201520162017
Citations per Year

Citation Velocity: 17

Averaging 17 citations per year over the last 3 years.

Learn more about how we calculate this metric in our FAQ.

Cite this paper

@article{Li2015PI3KAKTmTORPI, title={PI3K/AKT/mTOR pathway is activated after imatinib secondary resistance in gastrointestinal stromal tumors (GISTs).}, author={Jian Li and Yunzhi Dang and Jing Gao and Yanyan Li and Jianling Zou and Lin Shen}, journal={Medical oncology}, year={2015}, volume={32 4}, pages={111} }