PI3K-AKT-mTOR信号通路抑制剂与肿瘤免疫治疗

被引：37

作者：

赵家义

韩一平

机构：

[1] 第二军医大学附属长海医院呼吸与危重症医学科

来源：

中国肿瘤生物治疗杂志 | 2017年 / 24卷 / 12期

关键词：

PI3K-AKT-mTOR; 抑制剂; 肿瘤; 免疫治疗;

D O I：

暂无

中图分类号：

R730.51 [免疫疗法];

学科分类号：

100108 [医学免疫学];

摘要：

磷脂酰肌醇3-蛋白激酶B-哺乳动物雷帕霉素靶蛋白(PI3K-AKT-mTOR)信号通路的上游通路主要包括表皮生长因子受体(EGFR)、人类表皮生长因子受体2(HER2)、肝细胞生长因子受体(MET)和成纤维细胞生长因子受体(FGFR)等各类受体的酪氨酸激酶,其受体的突变、扩增常会导致PI3K-AKT-mTOR信号通路的失调,引起肿瘤发生发展。该通路异常激活常伴随着下游关键分子的改变包括PIK3CA、AKT1、PTEN的基因突变,PIK3CA、AKT1、AKT2的基因扩增,肿瘤抑制基因PTEN的缺失等。PI3K-AKT-mTOR信号通路抑制剂主要包括PI3K抑制剂、AKT抑制剂、mTOR抑制剂和双重抑制剂等。PI3K-AKT-mTOR抑制剂对肿瘤免疫微环境、免疫细胞均有显著影响。PI3K-AKT-mTOR抑制剂单药治疗肿瘤具有一定局限性,如联合DC疫苗、免疫检查点抑制剂和CAR-T细胞等免疫疗法可增强抗肿瘤疗效。

引用

收藏

页码：1424 / 1430

页数：7

相关论文

共 15 条

[1]

PI3K/AKT/mTOR信号通路在垂体腺瘤中的研究进展.[J].代从新;刘小海;孙博文;王任直;.中华医学杂志.2014, 09

[2]

Inhibition of mTOR kinase as a therapeutic target for acute myeloid leukemia [J].

Tabe, Yoko ;

Tafuri, Agostino ;

Sekihara, Kazumasa ;

Yang, Haeun ;

Konopleva, Marina .

EXPERT OPINION ON THERAPEUTIC TARGETS, 2017, 21 (07) :705-714

[3]

Tregs restrain dendritic cell autophagy to ameliorate autoimmunity [J].

Alissafi, Themis ;

Banos, Aggelos ;

Boon, Louis ;

Sparwasser, Tim ;

Ghigo, Alessandra ;

Wing, Kajsa ;

Vassilopoulos, Dimitrios ;

Boumpas, Dimitrios ;

Chavakis, Triantafyllos ;

Cadwell, Ken ;

Verginis, Panayotis .

JOURNAL OF CLINICAL INVESTIGATION, 2017, 127 (07) :2789-2804

[4]

Signaling by the Phosphoinositide 3-Kinase Family in Immune Cells.[J].Klaus Okkenhaug.Annual Review of Immunology.2013, 1

[5]

Posttranscriptional Control of T Cell Effector Function by Aerobic Glycolysis [J].

Chang, Chih-Hao ;

Curtis, Jonathan D. ;

Maggi, Leonard B., Jr. ;

Faubert, Brandon ;

Villarino, Alejandro V. ;

O'Sullivan, David ;

Huang, Stanley Ching-Cheng ;

van der Windt, Gerritje J. W. ;

Blagih, Julianna ;

Qiu, Jing ;

Weber, Jason D. ;

Pearce, Edward J. ;

Jones, Russell G. ;

Pearce, Erika L. .

CELL, 2013, 153 (06) :1239-1251

[6]

BAY 80-6946 Is a Highly Selective Intravenous PI3K Inhibitor with Potent p110α and p110δ Activities in Tumor Cell Lines and Xenograft Models [J].

Liu, Ningshu ;

Rowley, Bruce R. ;

Bull, Cathy O. ;

Schneider, Claudia ;

Haegebarth, Andrea ;

Schatz, Christoph A. ;

Fracasso, Paul R. ;

Wilkie, Dean P. ;

Hentemann, Martin ;

Wilhelm, Scott M. ;

Scott, William J. ;

Mumberg, Dominik ;

Ziegelbauer, Karl .

MOLECULAR CANCER THERAPEUTICS, 2013, 12 (11) :2319-2330

[7]

Receptor Tyrosine Kinases and TLR/IL1 Rs Unexpectedly Activate Myeloid Cell PI3Kγ, A Single Convergent Point Promoting Tumor Inflammation and Progression [J].

Schmid, Michael C. ;

Avraamides, Christie J. ;

Dippold, Holly C. ;

Franco, Irene ;

Foubert, Philippe ;

Ellies, Lesley G. ;

Acevedo, Lissette M. ;

Manglicmot, Joan R. E. ;

Song, Xiaodan ;

Wrasidlo, Wolfgang ;

Blair, Sara L. ;

Ginsberg, Mark H. ;

Cheresh, David A. ;

Hirsch, Emilio ;

Field, Seth J. ;

Varner, Judith A. .

CANCER CELL, 2011, 19 (06) :715-727

[8]

Discovery and biological activity of a novel class I PI3K inhibitor, CH5132799 [J].

Ohwada, Jun ;

Ebiike, Hirosato ;

Kawada, Hatsuo ;

Tsukazaki, Masao ;

Nakamura, Mitsuaki ;

Miyazaki, Takuya ;

Morikami, Kenji ;

Yoshinari, Kiyoshi ;

Yoshida, Miyuki ;

Kondoh, Osamu ;

Kuramoto, Shino ;

Ogawa, Kotaro ;

Aoki, Yuko ;

Shimma, Nobuo .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2011, 21 (06) :1767-1772

[9]

Hallmarks of Cancer: The Next Generation [J].

Hanahan, Douglas ;

Weinberg, Robert A. .

CELL, 2011, 144 (05) :646-674

[10]

TOR complex 2: a signaling pathway of its own [J].

Cybulski, Nadine ;

Hall, Michael N. .

TRENDS IN BIOCHEMICAL SCIENCES, 2009, 34 (12) :620-627