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dc.contributor.authorNeuzillet, Cen_US
dc.contributor.authorde Mestier, Len_US
dc.contributor.authorRousseau, Ben_US
dc.contributor.authorMir, Oen_US
dc.contributor.authorHebbar, Men_US
dc.contributor.authorKocher, HMen_US
dc.contributor.authorRuszniewski, Pen_US
dc.contributor.authorTournigand, Cen_US
dc.description.abstractUntil the 1990s, cytotoxic chemotherapy has been the cornerstone of medical therapy for gastrointestinal (GI) cancers. Better understanding of the cancer cell molecular biology has led to the therapeutic revolution of targeted therapies, i.e. monoclonal antibodies or small molecule inhibitors directed against proteins that are specifically overexpressed or mutated in cancer cells. These agents, being more specific to cancer cells, were expected to be less toxic than conventional cytotoxic agents. However, their effects have sometimes been disappointing, due to intrinsic or acquired resistance mechanisms, or to an activity restricted to some tumour settings, illustrating the importance of patient selection and early identification of predictive biomarkers of response to these therapies. Targeted agents have provided clinical benefit in many GI cancer types. Particularly, some GI tumours are considered chemoresistant and targeted therapies have offered a new therapeutic base for their management. Hence, somatostatin receptor-directed strategies, sorafenib, and imatinib have revolutioned the management of neuroendocrine tumours (NET), hepatocellular carcinoma (HCC), and gastrointestinal stromal tumours (GIST), respectively, and are now used as first-line treatment in many patients affected by these tumours. However, these agents face problems of resistances and identification of predictive biomarkers from imaging and/or biology. We propose a comprehensive two-part review providing a panoramic approach of the successes and failures of targeted agents in GI cancers to unravel the pharmacologic opportunities and future directions for these agents in GI oncology. In this second part, we will focus on NET, HCC, and GIST, whose treatment relies primarily on targeted therapies.en_US
dc.format.extent49 - 75en_US
dc.relation.ispartofPharmacol Theren_US
dc.rights© 2017. This manuscript version is made available under the CC-BY-NC-ND 4.0 license
dc.subjectmTOR inhibitorsen_US
dc.subjectAntibodies, Monoclonalen_US
dc.subjectAntineoplastic Agentsen_US
dc.subjectBiomarkers, Tumoren_US
dc.subjectCarcinoma, Hepatocellularen_US
dc.subjectGastrointestinal Neoplasmsen_US
dc.subjectLiver Neoplasmsen_US
dc.subjectMolecular Targeted Therapyen_US
dc.subjectNeuroendocrine Tumorsen_US
dc.titleUnravelling the pharmacologic opportunities and future directions for targeted therapies in gastro-intestinal cancers part 2: Neuroendocrine tumours, hepatocellular carcinoma, and gastro-intestinal stromal tumours.en_US
dc.rights.holder© 2017 Elsevier Inc.
pubs.notesNo embargoen_US

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