Publication

Primary and secondary kinase genotypes correlate with the biological and clinical activity of sunitinib in imatinib-resistant gastrointestinal stromal tumor.

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J Clin Oncol2008PMID 18955458PMC2651076stubpubmedPublished

Abstract

Abstract (excerpt)

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Linked entities

Linked entities (19)

How each link was made (MeSH, dictionary, registry reference, curation…) and whether it has been validated. Candidate links are not counted in entity statistics.

Validated 19

cancerGastrointestinal Stromal Tumorcivic_curation1.00
cancerMalignant Neoplasmcivic_curation1.00
drugImatinib Mesylatecivic_curation1.00
drugSunitinibcivic_curation1.00
geneKITcivic_curation1.00
genePDGFRAcivic_curation1.00
variantKIT A502_Y503insAYcivic_curation1.00
variantKIT D579delcivic_curation1.00
variantKIT Exon 11 Mutationcivic_curation1.00
variantKIT Exon 9 Mutationcivic_curation1.00
variantKIT K550_K558delcivic_curation1.00
variantKIT K550_K559DELcivic_curation1.00
variantKIT K558_V559delcivic_curation1.00
variantKIT L576Pcivic_curation1.00
variantKIT V555_V559DELcivic_curation1.00
variantKIT V560Dcivic_curation1.00
variantKIT W557_K558delcivic_curation1.00
variantPDGFRA D842Vcivic_curation1.00
variantPDGFRA V561Dcivic_curation1.00

Curated evidence

Evidence citing this paper (30)

civicCuratedShowing 1–30 of 30 evidence items · levels, directions and significance as curated at the source; each row links to its CIViC record.

Therapy	Cancer	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
KIT D579del1
Sunitinib	Gastrointestinal Stromal Tumor	Predictive	C	Supports Resistance	2	accepted	EID4142 Patient 74 from a larger cohort of genotyped patients (n= 78) with imatinib resistant or intolerant gastrointestinal stromal tumors (GISTs) harbored a primary (pre-imatinib treatment) KIT D579 deletio… (full text at CIViC) PMID 18955458 · Heinrich et al., 2008 · Open in CIViC	civic
KIT Exon 11 Mutation1
Sunitinib	Gastrointestinal Stromal Tumor	Predictive	B	Supports Resistance	3	accepted	EID4072 In a phase I/II trial of sunitinib efficacy on imatinib resistant or intolerant gastrointestinal stromal tumor (GIST) patients (n=77), patients harboring primary (pre-imatinib treatment) KIT exon 11 m… (full text at CIViC) PMID 18955458 · Heinrich et al., 2008 · Open in CIViC	civic
KIT Exon 9 Mutation1
Sunitinib	Gastrointestinal Stromal Tumor	Predictive	B	Supports Sensitivity Response	3	accepted	EID1424 In a study of 78 patients with gastrointestinal stromal tumors treated with sunitinib, patients with Kit exon 9 mutations or wildtype (lacking KIT or PDGFRA mutations) showed increased progression fre… (full text at CIViC) PMID 18955458 · Heinrich et al., 2008 · Open in CIViC	civic
KIT K550_K558del1
Sunitinib	Gastrointestinal Stromal Tumor	Predictive	C	Supports Resistance	2	accepted	EID4062 Patient 3 from a larger cohort of genotyped patients (n= 78) with imatinib resistant or intolerant gastrointestinal stromal tumors (GISTs) harbored a primary (pre-imatinib treatment) KIT K550_K558 del… (full text at CIViC) PMID 18955458 · Heinrich et al., 2008 · Open in CIViC	civic
KIT K550_K559DEL1
Sunitinib	Gastrointestinal Stromal Tumor	Predictive	C	Does Not Support Resistance	2	accepted	EID7289 Patient 78 from a larger cohort of genotyped patients (n= 78) with imatinib resistant or intolerant gastrointestinal stromal tumors (GISTs) harbored a primary (pre-imatinib treatment) KIT K550_V559 de… (full text at CIViC) PMID 18955458 · Heinrich et al., 2008 · Open in CIViC	civic
KIT K558delinsNP1
Sunitinib	Gastrointestinal Stromal Tumor	Predictive	C	Supports Resistance	—	submitted	EID4591 In a phase 1/2 trial of 97 gastrointestinal stromal tumor patients, patients with KIT exon 11 mutations (44/77) treated with sunitinib were associated with shorter progression free survival (5.1mo vs.… (full text at CIViC) PMID 18955458 · Heinrich et al., 2008 · Open in CIViC	civic
KIT K558_V559del1
Sunitinib	Gastrointestinal Stromal Tumor	Predictive	C	Supports Resistance	2	accepted	EID4095 Patient 47 from a larger cohort of genotyped patients (n= 78) with imatinib resistant or intolerant gastrointestinal stromal tumors (GISTs) harbored a primary (pre-imatinib treatment) KIT K558_V559 de… (full text at CIViC) PMID 18955458 · Heinrich et al., 2008 · Open in CIViC	civic
KIT L576P1
Sunitinib	Gastrointestinal Stromal Tumor	Predictive	C	Supports Resistance	2	accepted	EID4136 Patient 29 from a larger cohort of genotyped patients (n= 78) with imatinib resistant or intolerant gastrointestinal stromal tumors (GISTs) harbored a primary (pre-imatinib treatment) KIT L576P mutati… (full text at CIViC) PMID 18955458 · Heinrich et al., 2008 · Open in CIViC	civic
KIT P551_E554delPMYE1
Sunitinib	Gastrointestinal Stromal Tumor	Predictive	C	Supports Resistance	—	submitted	EID4453 In a phase 1/2 trial of 97 gastrointestinal stromal tumor patients, patients with KIT exon 11 mutations (44/77) treated with sunitinib were associated with shorter progression free survival (5.1mo vs.… (full text at CIViC) PMID 18955458 · Heinrich et al., 2008 · Open in CIViC	civic
KIT S501_A502INSAY1
Imatinib	Gastrointestinal Stromal Tumor	Predictive	B	Supports Resistance	—	submitted	EID2859 When transiently transfected into Chinese hamster ovary cells, the KIT exon 9 mutants were ten times less sensitive to imatinib in comparison to the KIT exon 11 mutants as measured by autophosphorylat… (full text at CIViC) PMID 18955458 · Heinrich et al., 2008 · Open in CIViC	civic
KIT V555_V559DEL1
Sunitinib	Gastrointestinal Stromal Tumor	Predictive	C	Supports Resistance	2	accepted	EID7288 Patient 36 from a larger cohort of genotyped patients (n= 78) with imatinib resistant or intolerant gastrointestinal stromal tumors (GISTs) harbored a primary (pre-imatinib treatment) KIT V555_V559 de… (full text at CIViC) PMID 18955458 · Heinrich et al., 2008 · Open in CIViC	civic
KIT V559D1
Sunitinib	Gastrointestinal Stromal Tumor	Predictive	C	Supports Resistance	—	submitted	EID4108 In a phase 1/2 trial of 97 gastrointestinal stromal tumor patients, patients with KIT exon 11 mutations (44/77) treated with sunitinib were associated with shorter progression free survival (5.1mo vs.… (full text at CIViC) PMID 18955458 · Heinrich et al., 2008 · Open in CIViC	civic
KIT V560D3
Sunitinib	Gastrointestinal Stromal Tumor	Predictive	C	Supports Resistance	3	accepted	EID4122 Patient 72 from a larger cohort of genotyped patients (n= 78) with imatinib resistant or intolerant gastrointestinal stromal tumors (GISTs) harbored a primary (pre-imatinib treatment) KIT V560D mutati… (full text at CIViC) PMID 18955458 · Heinrich et al., 2008 · Open in CIViC	civic
Imatinib Mesylate	Malignant NeoplasmALIAS	Predictive	D	Supports Sensitivity Response	2	accepted	EID5348 In an in vitro study, Chinese hamster ovary cells expressing KIT V560D mutation demonstrated sensitivity to imatinib treatment (IC50 = 100 vs IC50 = 1000) when compared to Chinese hamster ovary cells … (full text at CIViC) PMID 18955458 · Heinrich et al., 2008 · Open in CIViC	civic
Sunitinib	Malignant NeoplasmALIAS	Predictive	D	Does Not Support Resistance	2	accepted	EID4077 In an in vitro study, Chinese hamster ovary cells expressing KIT V560D demonstrated comparable sensitivity to sunitinib treatment compared to cells expressing ligand activated wild-type KIT (IC50<100 … (full text at CIViC) PMID 18955458 · Heinrich et al., 2008 · Open in CIViC	civic
KIT V560DEL1
Sunitinib	Gastrointestinal Stromal Tumor	Predictive	C	Supports Resistance	—	submitted	EID4117 In a phase 1/2 trial of 97 gastrointestinal stromal tumor patients, patients with KIT exon 11 mutations (44/77) treated with sunitinib were associated with shorter progression free survival (5.1mo vs.… (full text at CIViC) PMID 18955458 · Heinrich et al., 2008 · Open in CIViC	civic
KIT V560G1
Sunitinib	Gastrointestinal Stromal Tumor	Predictive	C	Supports Resistance	—	submitted	EID4129 In a phase 1/2 trial of 97 gastrointestinal stromal tumor patients, patients with KIT exon 11 mutations (44/77) treated with sunitinib were associated with shorter progression free survival (5.1mo vs.… (full text at CIViC) PMID 18955458 · Heinrich et al., 2008 · Open in CIViC	civic
KIT V569_L576DEL1
Sunitinib	Gastrointestinal Stromal Tumor	Predictive	C	Supports Resistance	—	submitted	EID4602 In a phase 1/2 trial of 97 gastrointestinal stromal tumor patients, patients with KIT exon 11 mutations (44/77) treated with sunitinib were associated with shorter progression free survival (5.1mo vs.… (full text at CIViC) PMID 18955458 · Heinrich et al., 2008 · Open in CIViC	civic
KIT W557_E561del1
Sunitinib	Gastrointestinal Stromal Tumor	Predictive	C	Supports Resistance	—	submitted	EID4090 In a phase 1/2 trial of 97 gastrointestinal stromal tumor patients, patients with KIT exon 11 mutations (44/77) treated with sunitinib were associated with shorter progression free survival (5.1mo vs.… (full text at CIViC) PMID 18955458 · Heinrich et al., 2008 · Open in CIViC	civic
KIT W557_K558del1
Sunitinib	Gastrointestinal Stromal Tumor	Predictive	C	Supports Resistance	3	accepted	EID4082 Patients 11, 69, and 73 from a larger cohort of genotyped patients (n= 78) with imatinib resistant or intolerant gastrointestinal stromal tumors (GISTs) harbored a primary (pre-imatinib treatment) KIT… (full text at CIViC) PMID 18955458 · Heinrich et al., 2008 · Open in CIViC	civic
KIT W557_V559insC1
Sunitinib	Gastrointestinal Stromal Tumor	Predictive	C	Supports Resistance	—	submitted	EID4460 In a phase 1/2 trial of 97 gastrointestinal stromal tumor patients, patients with KIT exon 11 mutations (44/77) treated with sunitinib were associated with shorter progression free survival (5.1mo vs.… (full text at CIViC) PMID 18955458 · Heinrich et al., 2008 · Open in CIViC	civic
KIT Y553_K558DEL1
Sunitinib	Gastrointestinal Stromal Tumor	Predictive	C	Supports Resistance	—	submitted	EID4067 In a phase 1/2 trial of 97 gastrointestinal stromal tumor patients, patients with KIT exon 11 mutations (44/77) treated with sunitinib were associated with shorter progression free survival (5.1mo vs.… (full text at CIViC) PMID 18955458 · Heinrich et al., 2008 · Open in CIViC	civic
KIT Y570_L576DEL1
Sunitinib	Gastrointestinal Stromal Tumor	Predictive	C	Supports Resistance	—	submitted	EID4586 In a phase 1/2 trial of 97 gastrointestinal stromal tumor patients, patients with KIT exon 11 mutations (44/77) treated with sunitinib were associated with shorter progression free survival (5.1mo vs.… (full text at CIViC) PMID 18955458 · Heinrich et al., 2008 · Open in CIViC	civic
PDGFRA D842V3
Sunitinib	Gastrointestinal Stromal Tumor	Predictive	C	Supports Resistance	3	accepted	EID4597 Patients 29 and 66 from a larger cohort of genotyped patients (n= 78) with imatinib resistant or intolerant gastrointestinal stromal tumors (GISTs) harbored a primary (pre-imatinib treatment) PDGFRA D… (full text at CIViC) PMID 18955458 · Heinrich et al., 2008 · Open in CIViC	civic
Imatinib Mesylate	Malignant NeoplasmALIAS	Predictive	D	Supports Resistance	2	accepted	EID5346 In an in vitro study, Chinese hamster ovary cells expressing PDGFRA D842V mutation demonstrated reduced sensitivity to imatinib treatment (IC50=2,500 vs. IC50<100), compared to Chinese hamster ovary c… (full text at CIViC) PMID 18955458 · Heinrich et al., 2008 · Open in CIViC	civic
Sunitinib	Malignant NeoplasmALIAS	Predictive	D	Supports Resistance	2	accepted	EID4060 In an in vitro study, Chinese hamster ovary cells expressing PDGFRA D842V mutation demonstrated reduced sensitivity to sunitinib treatment (IC50>1000 vs. IC50<100), compared to Chinese hamster ovary c… (full text at CIViC) PMID 18955458 · Heinrich et al., 2008 · Open in CIViC	civic
KIT A502_Y503insAY2
Imatinib	Malignant NeoplasmALIAS	Predictive	D	Supports Resistance	2	submitted	EID4505 In an in vitro study, Chinese hamster ovary cells expressing KIT A502_Y503INSAY demonstrated comparable resistance to imatinib treatment compared to CHO cells expressing ligand activated wild-type KIT… (full text at CIViC) PMID 18955458 · Heinrich et al., 2008 · Open in CIViC	civic
Sunitinib	Malignant NeoplasmALIAS	Predictive	D	Does Not Support Resistance	2	accepted	EID4100 In an in vitro study, Chinese hamster ovary cells expressing KIT A502_Y503INSAY demonstrated comparable sensitivity to sunitinib treatment compared to CHO cells expressing ligand activated wild-type K… (full text at CIViC) PMID 18955458 · Heinrich et al., 2008 · Open in CIViC	civic
PDGFRA V561D2
Imatinib Mesylate	Malignant NeoplasmALIAS	Predictive	D	Does Not Support Resistance	2	accepted	EID5347 In an in vitro study, Chinese hamster ovary cells expressing PDGFRA V561D mutation demonstrated sensitivity to imatinib treatment (IC50<100), though this sensitivity was indistinguishable from Chinese… (full text at CIViC) PMID 18955458 · Heinrich et al., 2008 · Open in CIViC	civic
Sunitinib	Malignant NeoplasmALIAS	Predictive	D	Does Not Support Resistance	2	accepted	EID4056 In an in vitro study, Chinese hamster ovary cells expressing PDGFRA V561D mutation demonstrated sensitivity to sunitinib treatment (IC50<100), though this sensitivity was indistinguishable from Chines… (full text at CIViC) PMID 18955458 · Heinrich et al., 2008 · Open in CIViC	civic