Drug Information

Drug (ID: DG01306) and It's Reported Resistant Information

• Name: Avapritinib
• Synonyms: Avapritinib; BLU-285; 1703793-34-3; Ayvakit; BLU285; (1S)-1-(4-fluorophenyl)-1-[2-[4-[6-(1-methylpyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-4-yl]piperazin-1-yl]pyrimidin-5-yl]ethanamine; UNII-513P80B4YJ; 513P80B4YJ; Ayvakyt; MFCD31544325; Avapritinib [INN]; Ayvakit (TN); Avapritinib (USAN/INN); Avapritinib (BLU-285); BLU-285 (Avapritinib); CHEMBL4204794; SCHEMBL16652297; GTPL10368; BLU 285; BDBM469269; AMY16753; EX-A1366; US10807985, Compound 44; NSC801082; s8553; AKOS037648993; CCG-269677; CS-7577; DB15233; NSC-801082; AC-31598; BB166456; BS-16206; HY-101561; C-366; 70C366; D11279; X720776; X-720776; Q29213676; (1S)-1-(4-Fluorophenyl)-1-(2-(4-(6-(1-methyl-1H-pyrazol-4-yl)pyrrolo(2,1-f)(1,2,4)triazin-4-yl)-1-piperazinyl)-5-pyrimidinyl)ethanamine; (S)-1-(4-Fluorophenyl)-1-(2-(4-(6-(1-methyl-1H-pyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-4-yl)piperazin-1-yl)pyrimidin-5-yl)ethan-1-amine; (S)-1-(4-fluorophenyl)-1-(2-(4-(6-(1-methyl-1H-pyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-4-yl)piperazin-1-yl)pyrimidin-5-yl)ethanamine
• Indication:
  In total 3 Indication(s)
  Gastrointestinal stromal tumour [ICD-11: 2B5B]; Approved; [1]
  Mast cell leukaemia [ICD-11: 2A21]; Approved; [1]
  Systemic mastocytosis [ICD-11: 2A21]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Gastrointestinal cancer [ICD-11: 2B5B]; [1]
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (2 diseases)
  Gastrointestinal cancer [ICD-11: 2B5B]; [2]
  Hematologic cancer [ICD-11: MG24]; [3]
• Target: Platelet-derived growth factor receptor alpha (PDGFRA); PGFRA_HUMAN; [1]
• Formula: C26H27FN10
• IsoSMILES: C[C@](C1=CC=C(C=C1)F)(C2=CN=C(N=C2)N3CCN(CC3)C4=NC=NN5C4=CC(=C5)C6=CN(N=C6)C)N
• InChI: 1S/C26H27FN10/c1-26(28,20-3-5-22(27)6-4-20)21-13-29-25(30-14-21)36-9-7-35(8-10-36)24-23-11-18(16-37(23)33-17-31-24)19-12-32-34(2)15-19/h3-6,11-17H,7-10,28H2,1-2H3/t26-/m0/s1
• InChIKey: DWYRIWUZIJHQKQ-SANMLTNESA-N
• PubChem CID: 118023034
• TTD Drug ID: D0UO2P

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

  RTDM: Regulation by the Disease Microenvironment

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-02: Benign/in-situ/malignant neoplasm

Solid tumour/cancer [ICD-11: 2A00-2F9Z]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [2]

• Molecule Alteration: Missense mutation; p.D816V (c.2447A>T)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: M230 cells; Skin; Homo sapiens (Human); CVCL_D749
• Experiment for Molecule Alteration: PCR
• Experiment for Drug Resistance: CellTiter-Glo assay; IC50 assay

Key Molecule: Platelet-derived growth factor receptor alpha (PDGFRA) [4]

• Molecule Alteration: Missense mutation; p.D842V (c.2525A>T)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Kasumi-1 cells; Peripheral blood; Homo sapiens (Human); CVCL_0589
• In Vitro Model: HMC-1.2 cells; Blood; Homo sapiens (Human); CVCL_H205
• In Vitro Model: P815 cells; N.A.; Mus musculus (Mouse); CVCL_2154
• In Vitro Model: M-07e cells; Peripheral blood; Homo sapiens (Human); CVCL_2106
• In Vitro Model: HMC-1.1 cells; Peripheral blood; Homo sapiens (Human); CVCL_H206
• In Vitro Model: Chinese hamster ovary (CHO)-K1 cells; Ovary; Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus); CVCL_0214
• In Vivo Model: BALB/c nude mouse PDX model; Mus musculus
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: Enzyme-linked immunosorbent assay; Cellular proliferation test assay

Mastocytosis [ICD-11: 2A21]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [5]

• Molecule Alteration: Missense mutation; p.V560G (c.1679T>G)
• Sensitive Disease: Mast cell neoplasm [ICD-11: 2A21.1]
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [6]

• Molecule Alteration: Synonymous; p.D816D (c.2448C>T)
• Sensitive Disease: Mastocytosis [ICD-11: 2A21.0]
• Experimental Note: Identified from the Human Clinical Data

Regulation by the Disease Microenvironment (RTDM)

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [4]

• Molecule Alteration: Missense mutation; p.V560G (c.1679T>G)
• Sensitive Disease: Mast cell leukaemia [ICD-11: 2A21.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Kasumi-1 cells; Peripheral blood; Homo sapiens (Human); CVCL_0589
• In Vitro Model: HMC-1.2 cells; Blood; Homo sapiens (Human); CVCL_H205
• In Vitro Model: P815 cells; N.A.; Mus musculus (Mouse); CVCL_2154
• In Vitro Model: M-07e cells; Peripheral blood; Homo sapiens (Human); CVCL_2106
• In Vitro Model: HMC-1.1 cells; Peripheral blood; Homo sapiens (Human); CVCL_H206
• In Vitro Model: Chinese hamster ovary (CHO)-K1 cells; Ovary; Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus); CVCL_0214
• In Vivo Model: BALB/c nude mouse PDX model; Mus musculus
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: Enzyme-linked immunosorbent assay; Cellular proliferation test assay

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [4]

• Molecule Alteration: Missense mutation; p.D816Y (c.2446G>T)
• Sensitive Disease: Mast cell neoplasm [ICD-11: 2A21.1]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Kasumi-1 cells; Peripheral blood; Homo sapiens (Human); CVCL_0589
• In Vitro Model: HMC-1.2 cells; Blood; Homo sapiens (Human); CVCL_H205
• In Vitro Model: P815 cells; N.A.; Mus musculus (Mouse); CVCL_2154
• In Vitro Model: M-07e cells; Peripheral blood; Homo sapiens (Human); CVCL_2106
• In Vitro Model: HMC-1.1 cells; Peripheral blood; Homo sapiens (Human); CVCL_H206
• In Vitro Model: Chinese hamster ovary (CHO)-K1 cells; Ovary; Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus); CVCL_0214
• In Vivo Model: BALB/c nude mouse PDX model; Mus musculus
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: Enzyme-linked immunosorbent assay; Cellular proliferation test assay

Acute myeloid leukemia [ICD-11: 2A60]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Regulation by the Disease Microenvironment (RTDM)

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [4]

• Molecule Alteration: Missense mutation; p.N822K (c.2466T>G)
• Sensitive Disease: Acute myeloid leukemia [ICD-11: 2A60.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Kasumi-1 cells; Peripheral blood; Homo sapiens (Human); CVCL_0589
• In Vitro Model: HMC-1.2 cells; Blood; Homo sapiens (Human); CVCL_H205
• In Vitro Model: P815 cells; N.A.; Mus musculus (Mouse); CVCL_2154
• In Vitro Model: M-07e cells; Peripheral blood; Homo sapiens (Human); CVCL_2106
• In Vitro Model: HMC-1.1 cells; Peripheral blood; Homo sapiens (Human); CVCL_H206
• In Vitro Model: Chinese hamster ovary (CHO)-K1 cells; Ovary; Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus); CVCL_0214
• In Vivo Model: BALB/c nude mouse PDX model; Mus musculus
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: Enzyme-linked immunosorbent assay; Cellular proliferation test assay

Hematologic cancer [ICD-11: 2B3Z]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Receptor-type tyrosine-protein kinase FLT3 (FLT3) [3]

• Molecule Alteration: Missense mutation; p.D835Y (c.2503G>T)
• Resistant Disease: Hematologic Cancer [ICD-11: MG24.Y]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: MV4-11 cells; Peripheral blood; Homo sapiens (Human); CVCL_0064
• In Vitro Model: MOLM14 cells; Peripheral blood; Homo sapiens (Human); CVCL_7916
• In Vivo Model: Female NCr-nude mouse model; Mus musculus
• Experiment for Drug Resistance: CellTiter-Glo assay; IC50 assay

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [3]

• Molecule Alteration: Missense mutation; p.D816V (c.2447A>T)
• Sensitive Disease: Hematologic Cancer [ICD-11: MG24.Y]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: MV4-11 cells; Peripheral blood; Homo sapiens (Human); CVCL_0064
• In Vitro Model: MOLM14 cells; Peripheral blood; Homo sapiens (Human); CVCL_7916
• In Vivo Model: Female NCr-nude mouse model; Mus musculus
• Experiment for Drug Resistance: CellTiter-Glo assay; IC50 assay

Gastrointestinal cancer [ICD-11: 2B5B]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [2]

• Molecule Alteration: Missense mutation; p.T670I (c.2009C>T)
• Resistant Disease: Gastrointestinal stromal tumor [ICD-11: 2B5B.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: M230 cells; Skin; Homo sapiens (Human); CVCL_D749
• Experiment for Molecule Alteration: PCR
• Experiment for Drug Resistance: CellTiter-Glo assay; IC50 assay

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [2]

• Molecule Alteration: Missense mutation; p.V654A (c.1961T>C)
• Resistant Disease: Gastrointestinal stromal tumor [ICD-11: 2B5B.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: M230 cells; Skin; Homo sapiens (Human); CVCL_D749
• Experiment for Molecule Alteration: PCR
• Experiment for Drug Resistance: CellTiter-Glo assay; IC50 assay

Key Molecule: Platelet-derived growth factor receptor alpha (PDGFRA) [1]

• Molecule Alteration: Missense mutation; p.V658A
• Resistant Disease: Gastrointestinal stromal tumor [ICD-11: 2B5B.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: U373 cells; Brain; Homo sapiens (Human); CVCL_2219
• In Vitro Model: NOMO1 cells; Bone marrow; Homo sapiens (Human); CVCL_1609
• In Vitro Model: Trsh1 cells; Stomach; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Whole genome sequencing assay
• Experiment for Drug Resistance: SRB assay
• Mechanism Description: Tumor and plasma biopsies in 6 of 7 patients with PDGFRA primary mutations who progressed on avapritinib or imatinib had secondary resistance mutations within PDGFRA exons 13, 14, and 15 that interfere with avapritinib binding. Secondary PDGFRA mutations causing V658A, N659K, Y676C, and G680R substitutions were found in 2 or more patients each, representing recurrent mechanisms of PDGFRA GIST drug resistance.

Key Molecule: Platelet-derived growth factor receptor alpha (PDGFRA) [1]

• Molecule Alteration: Missense mutation; p.N659K
• Resistant Disease: Gastrointestinal stromal tumor [ICD-11: 2B5B.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: U373 cells; Brain; Homo sapiens (Human); CVCL_2219
• In Vitro Model: NOMO1 cells; Bone marrow; Homo sapiens (Human); CVCL_1609
• In Vitro Model: Trsh1 cells; Stomach; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Whole genome sequencing assay
• Experiment for Drug Resistance: SRB assay
• Mechanism Description: Tumor and plasma biopsies in 6 of 7 patients with PDGFRA primary mutations who progressed on avapritinib or imatinib had secondary resistance mutations within PDGFRA exons 13, 14, and 15 that interfere with avapritinib binding. Secondary PDGFRA mutations causing V658A, N659K, Y676C, and G680R substitutions were found in 2 or more patients each, representing recurrent mechanisms of PDGFRA GIST drug resistance.

Key Molecule: Platelet-derived growth factor receptor alpha (PDGFRA) [1]

• Molecule Alteration: Missense mutation; p.Y676C
• Resistant Disease: Gastrointestinal stromal tumor [ICD-11: 2B5B.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: U373 cells; Brain; Homo sapiens (Human); CVCL_2219
• In Vitro Model: NOMO1 cells; Bone marrow; Homo sapiens (Human); CVCL_1609
• In Vitro Model: Trsh1 cells; Stomach; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Whole genome sequencing assay
• Experiment for Drug Resistance: SRB assay
• Mechanism Description: Tumor and plasma biopsies in 6 of 7 patients with PDGFRA primary mutations who progressed on avapritinib or imatinib had secondary resistance mutations within PDGFRA exons 13, 14, and 15 that interfere with avapritinib binding. Secondary PDGFRA mutations causing V658A, N659K, Y676C, and G680R substitutions were found in 2 or more patients each, representing recurrent mechanisms of PDGFRA GIST drug resistance.

Key Molecule: Platelet-derived growth factor receptor alpha (PDGFRA) [1]

• Molecule Alteration: Missense mutation; p.G680R
• Resistant Disease: Gastrointestinal stromal tumor [ICD-11: 2B5B.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: U373 cells; Brain; Homo sapiens (Human); CVCL_2219
• In Vitro Model: NOMO1 cells; Bone marrow; Homo sapiens (Human); CVCL_1609
• In Vitro Model: Trsh1 cells; Stomach; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Whole genome sequencing assay
• Experiment for Drug Resistance: SRB assay
• Mechanism Description: Tumor and plasma biopsies in 6 of 7 patients with PDGFRA primary mutations who progressed on avapritinib or imatinib had secondary resistance mutations within PDGFRA exons 13, 14, and 15 that interfere with avapritinib binding. Secondary PDGFRA mutations causing V658A, N659K, Y676C, and G680R substitutions were found in 2 or more patients each, representing recurrent mechanisms of PDGFRA GIST drug resistance.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [2]

• Molecule Alteration: Missense mutation; p.V560D (c.1679T>A)
• Sensitive Disease: Gastrointestinal stromal tumor [ICD-11: 2B5B.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: M230 cells; Skin; Homo sapiens (Human); CVCL_D749
• Experiment for Molecule Alteration: PCR
• Experiment for Drug Resistance: CellTiter-Glo assay; IC50 assay

Key Molecule: Platelet-derived growth factor receptor alpha (PDGFRA) [4]

• Molecule Alteration: Missense mutation; p.D842V (c.2525A>T)
• Sensitive Disease: Gastrointestinal stromal tumor [ICD-11: 2B5B.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Kasumi-1 cells; Peripheral blood; Homo sapiens (Human); CVCL_0589
• In Vitro Model: HMC-1.2 cells; Blood; Homo sapiens (Human); CVCL_H205
• In Vitro Model: P815 cells; N.A.; Mus musculus (Mouse); CVCL_2154
• In Vitro Model: M-07e cells; Peripheral blood; Homo sapiens (Human); CVCL_2106
• In Vitro Model: HMC-1.1 cells; Peripheral blood; Homo sapiens (Human); CVCL_H206
• In Vitro Model: Chinese hamster ovary (CHO)-K1 cells; Ovary; Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus); CVCL_0214
• In Vivo Model: BALB/c nude mouse PDX model; Mus musculus
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: Enzyme-linked immunosorbent assay; Cellular proliferation test assay

Regulation by the Disease Microenvironment (RTDM)

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [4]

• Molecule Alteration: Complex-indel; p.W557_V559delinsF (c.1670_1675delGGAAGG)
• Sensitive Disease: Gastrointestinal stromal tumor [ICD-11: 2B5B.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Kasumi-1 cells; Peripheral blood; Homo sapiens (Human); CVCL_0589
• In Vitro Model: HMC-1.2 cells; Blood; Homo sapiens (Human); CVCL_H205
• In Vitro Model: P815 cells; N.A.; Mus musculus (Mouse); CVCL_2154
• In Vitro Model: M-07e cells; Peripheral blood; Homo sapiens (Human); CVCL_2106
• In Vitro Model: HMC-1.1 cells; Peripheral blood; Homo sapiens (Human); CVCL_H206
• In Vitro Model: Chinese hamster ovary (CHO)-K1 cells; Ovary; Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus); CVCL_0214
• In Vivo Model: BALB/c nude mouse PDX model; Mus musculus
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: Enzyme-linked immunosorbent assay; Cellular proliferation test assay

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [4]

• Molecule Alteration: Missense mutation; p.D820V (c.2459A>T)
• Sensitive Disease: Gastrointestinal stromal tumor [ICD-11: 2B5B.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Kasumi-1 cells; Peripheral blood; Homo sapiens (Human); CVCL_0589
• In Vitro Model: HMC-1.2 cells; Blood; Homo sapiens (Human); CVCL_H205
• In Vitro Model: P815 cells; N.A.; Mus musculus (Mouse); CVCL_2154
• In Vitro Model: M-07e cells; Peripheral blood; Homo sapiens (Human); CVCL_2106
• In Vitro Model: HMC-1.1 cells; Peripheral blood; Homo sapiens (Human); CVCL_H206
• In Vitro Model: Chinese hamster ovary (CHO)-K1 cells; Ovary; Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus); CVCL_0214
• In Vivo Model: BALB/c nude mouse PDX model; Mus musculus
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: Enzyme-linked immunosorbent assay; Cellular proliferation test assay

References

• Ref 1: Resistance to Avapritinib in PDGFRA-Driven GIST Is Caused by Secondary Mutations in the PDGFRA Kinase Domain .Cancer Discov. 2021 Jan;11(1):108-125. doi: 10.1158/2159-8290.CD-20-0487. Epub 2020 Sep 24. 10.1158/2159-8290.CD-20-0487
• Ref 2: ATP-Competitive Inhibitors Midostaurin and Avapritinib Have Distinct Resistance Profiles in Exon 17-Mutant KITCancer Res. 2019 Aug 15;79(16):4283-4292. doi: 10.1158/0008-5472.CAN-18-3139. Epub 2019 Jul 3.
• Ref 3: Comparison of effects of midostaurin, crenolanib, quizartinib, gilteritinib, sorafenib and BLU-285 on oncogenic mutants of KIT, CBL and FLT3 in haematological malignanciesBr J Haematol. 2019 Nov;187(4):488-501. doi: 10.1111/bjh.16092. Epub 2019 Jul 15.
• Ref 4: A precision therapy against cancers driven by KIT/PDGFRA mutationsSci Transl Med. 2017 Nov 1;9(414):eaao1690. doi: 10.1126/scitranslmed.aao1690.
• Ref 5: Ripretinib (DCC-2618) Is a Switch Control Kinase Inhibitor of a Broad Spectrum of Oncogenic and Drug-Resistant KIT and PDGFRA VariantsCancer Cell. 2019 May 13;35(5):738-751.e9. doi: 10.1016/j.ccell.2019.04.006.
• Ref 6: Robust Activity of Avapritinib, Potent and Highly Selective Inhibitor of Mutated KIT, in Patient-derived Xenograft Models of Gastrointestinal Stromal TumorsClin Cancer Res. 2019 Jan 15;25(2):609-618. doi: 10.1158/1078-0432.CCR-18-1858. Epub 2018 Oct 1.