Emerging Agents for the Treatment of Advanced, Imatinib-Resistant Gastrointestinal Stromal Tumors : Current Status and Future Directions

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dc.contributor.author Bauer, Sebastian
dc.contributor.author Joensuu, Heikki
dc.date.accessioned 2017-08-16T12:09:01Z
dc.date.available 2017-08-16T12:09:01Z
dc.date.issued 2015-08
dc.identifier.citation Bauer , S & Joensuu , H 2015 , ' Emerging Agents for the Treatment of Advanced, Imatinib-Resistant Gastrointestinal Stromal Tumors : Current Status and Future Directions ' , Drugs , vol. 75 , no. 12 , pp. 1323-1334 . https://doi.org/10.1007/s40265-015-0440-8
dc.identifier.other PURE: 53229774
dc.identifier.other PURE UUID: 4deb014b-e953-49a3-b7e0-83a15a0d21ae
dc.identifier.other WOS: 000359445200002
dc.identifier.other Scopus: 84939266999
dc.identifier.other ORCID: /0000-0003-0281-2507/work/29959753
dc.identifier.uri http://hdl.handle.net/10138/212223
dc.description.abstract Imatinib is strongly positioned as the recommended first-line agent for most patients with advanced gastrointestinal stromal tumor (GIST) due to its good efficacy and tolerability. Imatinib-resistant advanced GIST continues to pose a therapeutic challenge, likely due to the frequent presence of multiple mutations that confer drug resistance. Sunitinib and regorafenib are approved as second- and third-line agents, respectively, for patients whose GIST does not respond to imatinib or who do not tolerate imatinib, and their use is supported by large randomized trials. ATP-mimetic tyrosine kinase inhibitors provide clinical benefit even in heavily pretreated GIST suggesting that oncogenic dependency on KIT frequently persists. Several potentially useful tyrosine kinase inhibitors with distinct inhibitory profiles against both KIT ATP-binding domain and activation loop mutations have not yet been fully evaluated. Agents that have been found promising in preclinical models and early clinical trials include small molecule KIT and PDGFRA mutation-specific inhibitors, heat shock protein inhibitors, histone deacetylase inhibitors, allosteric KIT inhibitors, KIT and PDGFRA signaling pathway inhibitors, and immunological approaches including antibody-drug conjugates. Concomitant or sequential administration of tyrosine kinase inhibitors with KIT signaling pathway inhibitors require further evaluation, as well as rotation of tyrosine kinase inhibitors as a means to suppress drug-resistant cell clones. en
dc.format.extent 12
dc.language.iso eng
dc.relation.ispartof Drugs
dc.rights cc_by
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject KIT TYROSINE KINASE
dc.subject PHASE-II
dc.subject C-KIT
dc.subject HSP90 INHIBITOR
dc.subject PROGNOSTIC-FACTORS
dc.subject ADJUVANT IMATINIB
dc.subject RANDOMIZED-TRIAL
dc.subject DRUG-RESISTANCE
dc.subject BRAF MUTATIONS
dc.subject DOSE IMATINIB
dc.subject 3122 Cancers
dc.subject 317 Pharmacy
dc.title Emerging Agents for the Treatment of Advanced, Imatinib-Resistant Gastrointestinal Stromal Tumors : Current Status and Future Directions en
dc.type Article
dc.contributor.organization Clinicum
dc.contributor.organization Heikki Joensuu / Principal Investigator
dc.contributor.organization Department of Oncology
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.1007/s40265-015-0440-8
dc.relation.issn 0012-6667
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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