Drug (ID: DG01687) and It's Reported Resistant Information
Name
Selumetinib/Dactolisib
Synonyms
Selumetinib/Dactolisib
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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
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Colorectal cancer [ICD-11: 2B91]
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: GTPase KRas (KRAS) [2]
Molecule Alteration Missense mutation
p.A146V (c.437C>T)
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Liver N.A.
In Vivo Model Female nonobese diabetic/severe combined immunodeficient (NOD/SCID) mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
Immunohistochemistry assay
Mechanism Description The missense mutation p.A146V (c.437C>T) in gene KRAS cause the sensitivity of Selumetinib + Dactolisib by unusual activation of pro-survival pathway
Key Molecule: GTPase KRas (KRAS) [2]
Molecule Alteration Missense mutation
p.G12C (c.34G>T)
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Liver N.A.
In Vivo Model Female nonobese diabetic/severe combined immunodeficient (NOD/SCID) mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
Immunohistochemistry assay
Mechanism Description The missense mutation p.G12C (c.34G>T) in gene KRAS cause the sensitivity of Selumetinib + Dactolisib by unusual activation of pro-survival pathway
Key Molecule: GTPase KRas (KRAS) [2]
Molecule Alteration Missense mutation
p.G12D (c.35G>A)
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Liver N.A.
In Vivo Model Female nonobese diabetic/severe combined immunodeficient (NOD/SCID) mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
Immunohistochemistry assay
Mechanism Description The missense mutation p.G12D (c.35G>A) in gene KRAS cause the sensitivity of Selumetinib + Dactolisib by unusual activation of pro-survival pathway
Key Molecule: GTPase KRas (KRAS) [2]
Molecule Alteration Missense mutation
p.G12V (c.35G>T)
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Liver N.A.
In Vivo Model Female nonobese diabetic/severe combined immunodeficient (NOD/SCID) mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
Immunohistochemistry assay
Mechanism Description The missense mutation p.G12V (c.35G>T) in gene KRAS cause the sensitivity of Selumetinib + Dactolisib by unusual activation of pro-survival pathway
Key Molecule: GTPase Nras (NRAS) [2]
Molecule Alteration Missense mutation
p.Q61K (c.181C>A)
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Liver N.A.
In Vivo Model Female nonobese diabetic/severe combined immunodeficient (NOD/SCID) mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
Immunohistochemistry assay
Mechanism Description The missense mutation p.Q61K (c.181C>A) in gene NRAS cause the sensitivity of Selumetinib + Dactolisib by unusual activation of pro-survival pathway
Melanoma [ICD-11: 2C30]
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [1]
Molecule Alteration Missense mutation
p.V600E (c.1799T>A)
Sensitive Disease Melanoma [ICD-11: 2C30.0]
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model BRAF-mutant melanoma cells N.A. Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
MTT assay
References
Ref 1 Primary cross-resistance to BRAFV600E-, MEK1/2- and PI3K/mTOR-specific inhibitors in BRAF-mutant melanoma cells counteracted by dual pathway blockadeOncotarget. 2016 Jan 26;7(4):3947-65. doi: 10.18632/oncotarget.6600.
Ref 2 Inhibition of MEK and PI3K/mTOR suppresses tumor growth but does not cause tumor regression in patient-derived xenografts of RAS-mutant colorectal carcinomasClin Cancer Res. 2012 May 1;18(9):2515-25. doi: 10.1158/1078-0432.CCR-11-2683. Epub 2012 Mar 5.

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