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Kimberly Kamp, Brenda Gumz, Richard A Feelders, Dik J Kwekkeboom, Gregory Kaltsas, Frederico P Costa and Wouter W de Herder

its use and some patients who initially responded may became refractory after a certain number of treatment cycles necessitating further treatment. Everolimus, an mTOR inhibitor, has been shown to be a promising anti-tumor agent for patients with well

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Elke Tatjana Aristizabal Prada, Vera Heinzle, Thomas Knösel, Svenja Nölting, Gerald Spöttl, Julian Maurer, Christine Spitzweg, Martin Angele, Nina Schmidt, Felix Beuschlein, Günter K Stalla, Rainer Blaser, Klaus A Kuhn and Christoph J Auernhammer

NETs are the mTORC1 inhibitor everolimus ( Pavel et al . 2011 , Yao et al . 2011 ) and the multi-tyrosin kinase inhibitor sunitinib ( Raymond et al . 2011 ) demonstrating the urgent need for innovative molecular therapeutic targets and strategies

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Maria Chiara Zatelli, Mariella Minoia, Chiara Martini, Federico Tagliati, Maria Rosaria Ambrosio, Marco Schiavon, Mattia Buratto, Fiorella Calabrese, Erica Gentilin, Giorgio Cavallesco, Lisa Berdondini, Federico Rea and Ettore C degli Uberti

reducing tumor growth ( Oberg & Jelic 2009 ), new therapeutic strategies are needed especially for aggressive tumors that cannot be radically treated with surgery. Everolimus, or RAD001, a novel oral mTOR inhibitor, has been recently employed in

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Elke Tatjana Aristizabal Prada, Gerald Spöttl, Julian Maurer, Michael Lauseker, Eva Jolanthe Koziolek, Jörg Schrader, Ashley Grossman, Karel Pacak, Felix Beuschlein, Christoph Joseph Auernhammer and Svenja Nölting

signaling pathway, which can be inhibited by the mTORC1 inhibitor everolimus ( Fig. 1 ) ( Zaytseva et al. 2012 , Wolin 2013 , Shipkova et al. 2016 ). The PI3K–Akt–mTORC1 axis is frequently over-activated in cancers, including panNETs, causing increased

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Jennifer A Chan, David P Ryan, Andrew X Zhu, Thomas A Abrams, Brian M Wolpin, Paige Malinowski, Eileen M Regan, Charles S Fuchs and Matthew H Kulke

. 2009 ). The side-effect profile of pasireotide LAR was also similar to that observed with s.c. pasireotide. The mTOR inhibitor everolimus is also associated with antitumor activity in patients with advanced neuroendocrine tumors. In initial phase II

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Barbara Mariniello, Antonio Rosato, Gaia Zuccolotto, Beatrice Rubin, Maria Verena Cicala, Isabella Finco, Maurizio Iacobone, Anna Chiara Frigo, Ambrogio Fassina, Raffaele Pezzani and Franco Mantero

linked to a decrease in production of VEGF and to a markedly inhibited response of vascular endothelial cells to stimulation by VEGF ( Guba et al . 2002 ). Everolimus, a derivative of rapamycin, acts as a signal transduction inhibitor. Its molecular

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Arvind Dasari, Alexandria Phan, Sanjay Gupta, Asif Rashid, Sai-Ching Jim Yeung, Kenneth Hess, Helen Chen, Emily Tarco, Huiqin Chen, Caimiao Wei, Kim Anh-Do, Daniel Halperin, Funda Meric-Bernstam and James Yao

associated with more aggressive tumors ( Meric-Bernstam & Gonzalez-Angulo 2009 , Jiao et al . 2011 ). The phase III randomized, placebo-controlled RADIANT-3 study showed significant improvement in progression-free survival (PFS) with everolimus, an oral

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James Yao, Abhishek Garg, David Chen, Jaume Capdevila, Paul Engstrom, Rodney Pommier, Eric Van Cutsem, Simron Singh, Nicola Fazio, Wei He, Markus Riester, Parul Patel, Maurizio Voi, Michael Morrissey, Marianne Pavel and Matthew Helmut Kulke

-controlled, phase 3 studies that evaluated the efficacy and safety of everolimus in distinct types of NET. These trials comprised the RADIANT-2 and RADIANT-4 trials in the GI and lung, and the RADIANT-3 trial in the pNET ( Pavel et al. 2011 , Yao et al. 2011

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Nan Liu, Sheng Tai, Boxiao Ding, Ryan K Thor, Sunita Bhuta, Yin Sun and Jiaoti Huang

rapamycin (mTOR) pathway is a major signaling pathway promoting cellular proliferation in many cancer types including ovarian cancer ( Bartholomeusz & Gonzalez-Angulo 2012 ). Rapamycin or its derivative, everolimus (we will refer to Rad001, which is a more

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Alexander Gorshtein, Hadara Rubinfeld, Efrat Kendler, Marily Theodoropoulou, Vesna Cerovac, Günter K Stalla, Zvi R Cohen, Moshe Hadani and Ilan Shimon

, lymphomas, melanomas, and CNS tumors ( Cantley & Neel 1999 , Simpson & Parsons 2001 ). Tumors bearing these mutations are particularly susceptible to mTOR inhibitors. Rapamycin analogs, such as RAD001 (Everolimus, Novartis Pharma), were shown to effectively