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Overcoming Resistance to Targeted Therapies: The Next Challenge in Pancreatic Neuroendocrine Tumors (PNETs) Treatment

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Book cover Management of Neuroendocrine Tumors of the Pancreas and Digestive Tract

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Abstract

Chemotherapy in pancreatic neuroendocrine tumors (PNET) has remained for decades the only validated therapeutic option, albeit with debated efficacy. Recently, data from two large placebo controlled phase III trials have changed the therapeutic landscape. They demonstrated that targeted therapies directed against receptor of vascular endothelial growth factor (VEGFR) (sunitinib) and mammalian target of rapamycin (mTOR) (everolimus) produced clinically significant improvement in patients with advanced PNETs, resulting in a doubling of progression-free survival and leading to FDA approval. However, with an increasing number of patients being treated with these drugs following their approval, resistance has emerged as a critical clinical issue. In this review, we aim to summarize the current knowledge about primary (i.e., early progression) and acquired (i.e., tumor regrowth after initial response) resistance to antiangiogenic agents and mTOR inhibitors, using data available from preclinical and clinical studies in various malignancies. Herein, we also describe how these general mechanisms of resistance may emerge in patients with PNET treated with sunitinib and everolimus. Overcoming such resistances is likely to be the next challenge for clinicians in advanced PNETs management, warranting seeking for new anticancer strategies.

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Author information

Authors and Affiliations

  1. AAREC Filia Research, 1 place Paul Verlaine, 92100, Boulogne, Billancourt, France

    Annemilaï Tijeras-Raballand, Maria Serova & Armand de Gramont

  2. Inserm U728-Medical Oncology Department, Beaujon University Hospital, 100 bd du general Leclerc, 92100, Paris, France

    Cindy Neuzillet, Maria Serova, Armand de Gramont & Eric Raymond

  3. Gastroenterology and Pancreatology Department, Beaujon University Hospital, 100 bd du general Leclerc, 92100, Paris, France

    Cindy Neuzillet & Pascal Hammel

  4. Pathology Department, Bichat University Hospital, 46, rue Henri Huchard, Paris Cedex 18, 75877, Paris, France

    Anne Couvelard

  5. Inserm U773-Medical Oncology Department, Beaujon University Hospital, 100 bd du general Leclerc, 92100, Paris, France

    Annemilaï Tijeras-Raballand & Sandrine Faivre

Authors
  1. Annemilaï Tijeras-Raballand
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  2. Cindy Neuzillet
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  3. Anne Couvelard
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  4. Maria Serova
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  5. Armand de Gramont
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  6. Pascal Hammel
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  7. Eric Raymond
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  8. Sandrine Faivre
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Corresponding author

Correspondence to Annemilaï Tijeras-Raballand .

Editor information

Editors and Affiliations

  1. Medical Oncology, Bichat-Beaujon University Hospitals, Clichy cedex, France

    Eric Raymond

  2. Bichat-Beaujon University Hospitals Medical Oncology, Clichy cedex, France

    Sandrine Faivre

  3. Pancreatology, Bichat-Beaujon University Hospitals Gastroenterology and, Clichy cedex, France

    Philippe Ruszniewski

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Tijeras-Raballand, A. et al. (2014). Overcoming Resistance to Targeted Therapies: The Next Challenge in Pancreatic Neuroendocrine Tumors (PNETs) Treatment. In: Raymond, E., Faivre, S., Ruszniewski, P. (eds) Management of Neuroendocrine Tumors of the Pancreas and Digestive Tract. Springer, Paris. https://doi.org/10.1007/978-2-8178-0430-9_12

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  • DOI: https://doi.org/10.1007/978-2-8178-0430-9_12

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  • Publisher Name: Springer, Paris

  • Print ISBN: 978-2-8178-0429-3

  • Online ISBN: 978-2-8178-0430-9

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