Targeting the mTOR pathway in breast cancer

被引:29
作者
Liu, Jia [1 ]
Li, Hui-Qing [1 ]
Zhou, Fu-Xia [1 ]
Yu, Jie-Wen [1 ]
Sun, Ling [1 ]
Han, Zhong-Hou [1 ]
机构
[1] Maternal & Child Hlth Hosp Qinhuangdao, 452 Hongqi Rd, Qinhuangdao 066000, Peoples R China
关键词
Mechanistic target of rapamycin; mechanistic target of rapamycin inhibitors; breast cancer; diagnostic biomarkers; clinical trials; REGULATES ESTROGEN-RECEPTOR; COMPLEX; MTORC1; PHOSPHATIDYLINOSITOL; 3-KINASE; NEOADJUVANT CHEMOTHERAPY; PI3K/AKT/MTOR PATHWAY; MAMMALIAN TARGET; TRASTUZUMAB-RESISTANT; THERAPEUTIC TARGET; KINASE INHIBITOR; PI3K INHIBITOR;
D O I
10.1177/1010428317710825
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Mechanistic target of rapamycin controls cell growth, metabolism, and aging in response to nutrients, cellular energy stage, and growth factors. In cancers including breast cancer, mechanistic target of rapamycin is frequently upregulated. Blocking mechanistic target of rapamycin with rapamycin, first-generation and second-generation mechanistic target of rapamycin inhibitors, called rapalogs, have shown potent reduction of breast cancer tumor growth in preclinical models and clinical trials. In this review, we summarize the fundamental role of the mechanistic target of rapamycin pathway in driving breast tumors. Moreover, we also review key molecules involved with aberrant mechanistic target of rapamycin pathway activation in breast cancer and current efforts to target these components for therapeutic gain. Further development of predictive biomarkers will be useful in the selection of patients who will benefit from inhibition of the mechanistic target of rapamycin pathway.
引用
收藏
页数:15
相关论文
共 120 条
[1]   Risk of fatigue and hepatic and metabolic toxicities in patients with solid tumors treated with everolimus: a meta-analysis [J].
Abdel-Rahman, Omar ;
Fouad, Mona .
FUTURE ONCOLOGY, 2015, 11 (01) :79-90
[2]   Impact of estrogen receptor (ER) and human epidermal growth factor receptor-2 (HER2) co-expression on breast cancer disease characteristics: implications for tumor biology and research [J].
Alqaisi, Abeer ;
Chen, Li ;
Romond, Edward ;
Chambers, Mara ;
Stevens, Mark ;
Pasley, Grace ;
Awasthi, Mukta ;
Massarweh, Suleiman .
BREAST CANCER RESEARCH AND TREATMENT, 2014, 148 (02) :437-444
[3]   Everolimus for women with trastuzumab-resistant, HER2-positive, advanced breast cancer (BOLERO-3): a randomised, double-blind, placebo-controlled phase 3 trial [J].
Andre, Fabrice ;
O'Regan, Ruth ;
Ozguroglu, Mustafa ;
Toi, Masakazu ;
Xu, Binghe ;
Jerusalem, Guy ;
Masuda, Norikazu ;
Wilks, Sharon ;
Arena, Francis ;
Isaacs, Claudine ;
Yap, Yoon-Sim ;
Papai, Zsuzsanna ;
Lang, Istvan ;
Armstrong, Anne ;
Lerzo, Guillermo ;
White, Michelle ;
Shen, Kunwei ;
Litton, Jennifer ;
Chen, David ;
Zhang, Yufen ;
Ali, Shyanne ;
Taran, Tetiana ;
Gianni, Luca .
LANCET ONCOLOGY, 2014, 15 (06) :580-591
[4]   A meta-analysis of oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 discordance between primary breast cancer and metastases [J].
Aurilio, Gaetano ;
Disalvatore, Davide ;
Pruneri, Giancarlo ;
Bagnardi, Vincenzo ;
Viale, Giuseppe ;
Curigliano, Giuseppe ;
Adamoli, Laura ;
Munzone, Elisabetta ;
Sciandivasci, Angela ;
De Vita, Fernando ;
Goldhirsch, Aron ;
Nole, Franco .
EUROPEAN JOURNAL OF CANCER, 2014, 50 (02) :277-289
[5]   STRUCTURAL BIOLOGY Architecture of human mTOR complex 1 [J].
Aylett, Christopher H. S. ;
Sauer, Evelyn ;
Imseng, Stefan ;
Boehringer, Daniel ;
Hall, Michael N. ;
Ban, Nenad ;
Maier, Timm .
SCIENCE, 2016, 351 (6268) :48-52
[6]   Randomized Phase II Trial of Everolimus in Combination With Tamoxifen in Patients With Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer With Prior Exposure to Aromatase Inhibitors: A GINECO Study [J].
Bachelot, Thomas ;
Bourgier, Celine ;
Cropet, Claire ;
Ray-Coquard, Isabelle ;
Ferrero, Jean-Marc ;
Freyer, Gilles ;
Abadie-Lacourtoisie, Sophie ;
Eymard, Jean-Christophe ;
Debled, Marc ;
Spaeth, Dominique ;
Legouffe, Eric ;
Allouache, Djelila ;
El Kouri, Claude ;
Pujade-Lauraine, Eric .
JOURNAL OF CLINICAL ONCOLOGY, 2012, 30 (22) :2718-2724
[7]   Everolimus in Postmenopausal Hormone-Receptor-Positive Advanced Breast Cancer [J].
Baselga, Jose ;
Campone, Mario ;
Piccart, Martine ;
Burris, Howard A., III ;
Rugo, Hope S. ;
Sahmoud, Tarek ;
Noguchi, Shinzaburo ;
Gnant, Michael ;
Pritchard, Kathleen I. ;
Lebrun, Fabienne ;
Beck, J. Thaddeus ;
Ito, Yoshinori ;
Yardley, Denise ;
Deleu, Ines ;
Perez, Alejandra ;
Bachelot, Thomas ;
Vittori, Luc ;
Xu, Zhiying ;
Mukhopadhyay, Pabak ;
Lebwohl, David ;
Hortobagyi, Gabriel N. .
NEW ENGLAND JOURNAL OF MEDICINE, 2012, 366 (06) :520-529
[8]   Phase II Randomized Study of Neoadjuvant Everolimus Plus Letrozole Compared With Placebo Plus Letrozole in Patients With Estrogen Receptor-Positive Breast Cancer [J].
Baselga, Jose ;
Semiglazov, Vladimir ;
van Dam, Peter ;
Manikhas, Alexey ;
Bellet, Meritxell ;
Mayordomo, Jose ;
Campone, Mario ;
Kubista, Ernst ;
Greil, Richard ;
Bianchi, Giulia ;
Steinseifer, Jutta ;
Molloy, Betty ;
Tokaji, Erika ;
Gardner, Humphrey ;
Phillips, Penny ;
Stumm, Michael ;
Lane, Heidi A. ;
Dixon, J. Michael ;
Jonat, Walter ;
Rugo, Hope S. .
JOURNAL OF CLINICAL ONCOLOGY, 2009, 27 (16) :2630-2637
[9]   Rapamycin passes the torch: a new generation of mTOR inhibitors [J].
Benjamin, Don ;
Colombi, Marco ;
Moroni, Christoph ;
Hall, Michael N. .
NATURE REVIEWS DRUG DISCOVERY, 2011, 10 (11) :868-880
[10]   PI3K-independent mTOR activation promotes lapatinib resistance and IAP expression that can be effectively reversed by mTOR and Hsp90 inhibition [J].
Brady, Samuel W. ;
Zhang, Jian ;
Tsai, Ming-Horng ;
Yu, Dihua .
CANCER BIOLOGY & THERAPY, 2015, 16 (03) :402-411