Drug Information

Drug (ID: DG01703) and It's Reported Resistant Information

• Name: G007-LK/Imatinib
• Synonyms: G007-LK/Imatinib
• Target: .; NOUNIPROTAC; [1]

Type(s) of Resistant Mechanism of This Drug

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

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

Gastrointestinal cancer [ICD-11: 2B5B]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [1]

• Molecule Alteration: IF-deletion; p.V560delV (c.1679_1681delTTG)
• Sensitive Disease: Gastrointestinal stromal tumor [ICD-11: 2B5B.0]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Wnt/Beta-catenin signaling pathway; Inhibition; hsa04310
• In Vitro Model: GIST882 cells; Gastric; Homo sapiens (Human); CVCL_7044
• In Vitro Model: S2 GIST cells; N.A.; Mus musculus (Mouse); N.A.
• In Vitro Model: GIST T1 cells; Pleural effusion; Homo sapiens (Human); CVCL_4976
• In Vivo Model: NSG mouse PDX model; Mus musculus
• Experiment for Molecule Alteration: RT-PCR; Immunohistochemistry assay; Western blotting analysis
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: Activation of the canonical Wnt pathway and accumulation of nuclear active beta-catenin were present in a subset of human GISTs that were treatment na ve, responsive to imatinib, or resistant to imatinib. The mechanism involved reduction of DKK4 and enhanced the nuclear beta-catenin stability by COP1 loss. Inhibiting Wnt/beta-catenin signaling alone or in combination with imatinib demonstrated anti-tumor efficacy in multiple cells and pre-clinical models in GIST.

References

• Ref 1: Wnt/Beta-catenin Signaling Contributes to Tumor Malignancy and Is Targetable in Gastrointestinal Stromal TumorMol Cancer Ther. 2017 Sep;16(9):1954-1966. doi: 10.1158/1535-7163.MCT-17-0139. Epub 2017 Jun 13.