In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 77, No. 13_Supplement ( 2017-07-01), p. 144-144
Abstract:
Activation of the PI3K pathway is commonly observed and is correlated with tumor development, progression, poor prognosis, and resistance to cancer therapies, such as radiotherapy, in most cancers. As a central node of this pathway, PI3K is an attractive target for PI3K-addicted cancer therapy and PI3K inhibitors may thus restore sensitivity to other treatments when administered as part of combination regimens. Here, we found that PI3K/p85 was expressed predominantly in the radioresistant head and neck cancer cell line (HN31 cell line). And then, we investigated whether PI3K modulation was crucial for the development of novel treatment strategies for radioresistant cancer cell line. Interestingly, we found that head and neck cancer cell lines with PI3K/p85 activation showed the resistance to PI3K inhibitors and the resistance mechanism was associated with Src activation which is a member of a superfamily of membrane-associated nonreceptor protein tyrosine kinases. Src inhibitor improves the efficacy of PI3K inhibitor treatment through suppression of Src and PI3K/p85 activation in HN31 cell line. Collectively, our study highlights the role of p85 and Src activation in the resistance for PI3K inhibition and the potential clinical application of combination regimens of Src and PI3K inhibitors in head and neck cancers. This is the first investigation to analyze the role of Src in resistance to the PI3K inhibitors of head and neck cancer. As a consequence, a greater understanding of resistance mechanisms through our results will enable the rational design of combination regimens and sequential treatment algorithms to improve clinical outcomes. Citation Format: Gui Chul Kim, Hae Yun Nam, Hyang Ju Lee, Min Kyung Kim, Geun Hee Lee, Myung Woul Han, Seong Who KIM, Sang Yoon Kim. Src leads to a novel mechanism of resistance to PI3K inhibitors through regulation of PI3K/p85 activation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 144. doi:10.1158/1538-7445.AM2017-144
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2017-144
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2017
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
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