Targeting PI3K Signaling in Combination Cancer Therapy

被引：126

作者：

Pons-Tostivint, Elvire ^{[1
,2
]}

Thibault, Benoit ^{[1
,2
]}

Guillermet-Guibert, Julie ^{[1
,2
]}

机构：

[1] Univ Toulouse III Paul Sabatier, CRCT, INSERM, Toulouse, France

[2] Lab Excellence LABEX TouCAN, Toulouse, France

来源：

TRENDS IN CANCER | 2017年 / 3卷 / 06期

关键词：

METASTATIC BREAST-CANCER; PHOSPHATIDYLINOSITOL 3-KINASE INHIBITOR; PANCREATIC-CELL PLASTICITY; 1ST-IN-HUMAN PHASE-I; BUPARLISIB BKM120; PIK3CA MUTATIONS; DOSE-ESCALATION; WILD-TYPE; TRASTUZUMAB RESISTANCE; PILARALISIB SAR245408;

D O I：

10.1016/j.trecan.2017.04.002

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Targeting upstream phosphatidylinositol-3-kinases (PI3Ks) in the PI3K/Akt/mTOR pathway appears to be a promising therapy in solid cancers; however, first early clinical trials with PI3K inhibitors in monotherapy have been disappointing. A massive array of preclinical and clinical trials are currently evaluating combinations of PI3K inhibitors in targeted therapies. These combinations include co-treatments with drugs directed against other intra-/extracellular signaling molecules, nuclear hormone receptors, DNA damage repair enzymes, and immune modulators. We review the literature and pinpoint mechanisms of action in different genomic and organ contexts. Combinatorial approaches are potentially superior to monotherapies and should become alternative clinical strategies to treat cancer patients.

引用

页码：454 / 469

页数：16

共 111 条

[51] A randomized, phase II trial of cetuximab with or without PX-866, an irreversible oral phosphatidylinositol 3-kinase inhibitor, in patients with relapsed or metastatic head and neck squamous cell cancer [J].

Jimeno, A. ;

Shirai, K. ;

Choi, M. ;

Laskin, J. ;

Kochenderfer, M. ;

Spira, A. ;

Cline-Burkhardt, V. ;

Winquist, E. ;

Hausman, D. ;

Walker, L. ;

Cohen, R. B. .

ANNALS OF ONCOLOGY, 2015, 26 (03) :556-561

[52] Fighting cancer drug resistance: Opportunities and challenges for mutation-specific EGFR inhibitors [J].

Juchum, Michael ;

Guenther, Marcel ;

Laufer, Stefan A. .

DRUG RESISTANCE UPDATES, 2015, 20 :12-28

[53] Ligand-Independent HER2/HER3/PI3K Complex Is Disrupted by Trastuzumab and Is Effectively Inhibited by the PI3K Inhibitor GDC-0941 [J].

Junttila, Teemu T. ;

Akita, Robert W. ;

Parsons, Kathryn ;

Fields, Carter ;

Phillips, Gail D. Lewis ;

Friedman, Lori S. ;

Sampath, Deepak ;

Sliwkowski, Mark X. .

CANCER CELL, 2009, 15 (05) :429-440

[54] Convergent loss of PTEN leads to clinical resistance to a PI(3)Kα inhibitor [J].

Juric, Dejan ;

Castel, Pau ;

Griffith, Malachi ;

Griffith, Obi L. ;

Won, Helen H. ;

Ellis, Haley ;

Ebbesen, Saya H. ;

Ainscough, Benjamin J. ;

Ramu, Avinash ;

Iyer, Gopa ;

Shah, Ronak H. ;

Huynh, Tiffany ;

Mino-Kenudson, Mari ;

Sgroi, Dennis ;

Isakoff, Steven ;

Thabet, Ashraf ;

Elamine, Leila ;

Solit, David B. ;

Lowe, ScottW. ;

Quadt, Cornelia ;

Peters, Malte ;

Derti, Adnan ;

Schegel, Robert ;

Huang, Alan ;

Mardis, Elaine R. ;

Berger, Michael F. ;

Baselga, Jose ;

Scaltriti, Maurizio .

NATURE, 2015, 518 (7538) :240-U230

[55] Combining a PI3K Inhibitor with a PARP Inhibitor Provides an Effective Therapy for BRCA1-Related Breast Cancer [J].

Juvekar, Ashish ;

Burga, Laura N. ;

Hu, Hai ;

Lunsford, Elaine P. ;

Ibrahim, Yasir H. ;

Balmana, Judith ;

Rajendran, Anbazhagan ;

Papa, Antonella ;

Spencer, Katherine ;

Lyssiotis, Costas A. ;

Nardella, Caterina ;

Pandolfi, Pier Paolo ;

Baselga, Jose ;

Scully, Ralph ;

Asara, John M. ;

Cantley, Lewis C. ;

Wulf, Gerburg M. .

CANCER DISCOVERY, 2012, 2 (11) :1048-1063

[56] Macrophage PI3Kγ Drives Pancreatic Ductal Adenocarcinoma Progression [J].

Kaneda, Megan M. ;

Cappello, Paola ;

Nguyen, Abraham V. ;

Ralainirina, Natacha ;

Hardamon, Chanae R. ;

Foubert, Philippe ;

Schmid, Michael C. ;

Sun, Ping ;

Mose, Evangeline ;

Bouvet, Michael ;

Lowy, Andrew M. ;

Valasek, Mark A. ;

Sasik, Roman ;

Novelli, Francesco ;

Hirsch, Emilio ;

Varner, Judith A. .

CANCER DISCOVERY, 2016, 6 (08) :870-885

[57]

Keam B, 2015, ANTICANCER RES, V35, P175

[58] Comprehensive molecular portraits of human breast tumours [J].

Koboldt, Daniel C. ;

Fulton, Robert S. ;

McLellan, Michael D. ;

Schmidt, Heather ;

Kalicki-Veizer, Joelle ;

McMichael, Joshua F. ;

Fulton, Lucinda L. ;

Dooling, David J. ;

Ding, Li ;

Mardis, Elaine R. ;

Wilson, Richard K. ;

Ally, Adrian ;

Balasundaram, Miruna ;

Butterfield, Yaron S. N. ;

Carlsen, Rebecca ;

Carter, Candace ;

Chu, Andy ;

Chuah, Eric ;

Chun, Hye-Jung E. ;

Coope, Robin J. N. ;

Dhalla, Noreen ;

Guin, Ranabir ;

Hirst, Carrie ;

Hirst, Martin ;

Holt, Robert A. ;

Lee, Darlene ;

Li, Haiyan I. ;

Mayo, Michael ;

Moore, Richard A. ;

Mungall, Andrew J. ;

Pleasance, Erin ;

Robertson, A. Gordon ;

Schein, Jacqueline E. ;

Shafiei, Arash ;

Sipahimalani, Payal ;

Slobodan, Jared R. ;

Stoll, Dominik ;

Tam, Angela ;

Thiessen, Nina ;

Varhol, Richard J. ;

Wye, Natasja ;

Zeng, Thomas ;

Zhao, Yongjun ;

Birol, Inanc ;

Jones, Steven J. M. ;

Marra, Marco A. ;

Cherniack, Andrew D. ;

Saksena, Gordon ;

Onofrio, Robert C. ;

Pho, Nam H. .

NATURE, 2012, 490 (7418) :61-70

[59] Pictilisib for oestrogen receptor-positive, aromatase inhibitor-resistant, advanced or metastatic breast cancer (FERGI): a randomised, double-blind, placebo-controlled, phase 2 trial [J].

Krop, Ian E. ;

Mayer, Ingrid A. ;

Ganju, Vinod ;

Dickler, Maura ;

Johnston, Stephen ;

Morales, Serafi N. ;

Yardley, Denise A. ;

Melichar, Bohuslav ;

Forero-Torres, Andres ;

Lee, Soo Chin ;

de Boer, Richard ;

Petrakova, Katarina ;

Vallentin, Susanne ;

Perez, Edith A. ;

Piccart, Martine ;

Ellis, Matthew ;

Winer, Eric ;

Gendreau, Steven ;

Derynck, Mika ;

Lackner, Mark ;

Levy, Gallia ;

Qiu, Jiaheng ;

He, Jing ;

Schmid, Peter .

LANCET ONCOLOGY, 2016, 17 (06) :811-821

[60] Treatment effect of buparlisib, cetuximab and irradiation in wild-type or PI3KCA-mutated head and neck cancer cell lines [J].

Lattanzio, Laura ;

Tonissi, Federica ;

Monteverde, Martino ;

Vivenza, Daniela ;

Russi, Elvio ;

Milano, Gerard ;

Merlano, Marco ;

Lo Nigro, Cristiana .

INVESTIGATIONAL NEW DRUGS, 2015, 33 (02) :310-320

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