Drug Information

Drug (ID: DG01689) and It's Reported Resistant Information

• Name: Everolimus/Selumetinib
• Synonyms: Everolimus/Selumetinib
• 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

Brain cancer [ICD-11: 2A00]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [1]

• Molecule Alteration: Missense mutation; p.V600E (c.1799T>A)
• Sensitive Disease: Brain glioma [ICD-11: 2A00.0]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: BRAF/MEK/MAPK signaling pathway; Inhibition; hsa04010
• In Vitro Model: DBTRG cells; Brain; Homo sapiens (Human); CVCL_1169
• In Vitro Model: SF9427 cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: SF8628 cells; Brain; Homo sapiens (Human); CVCL_IT46
• In Vitro Model: SF188 cells; Brain; Homo sapiens (Human); CVCL_6948
• In Vitro Model: BT40 cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: AM-38 cells; Brain; Homo sapiens (Human); CVCL_1070
• In Vivo Model: NSG mouse PDX model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: Combination therapy in BRAFV600E-mutant human glioma cells enhances cell cycle arrest and apoptosis and reduces proliferation compared to monotherapy.

Lung cancer [ICD-11: 2C25]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: GTPase Hras (HRAS) [2]

• Molecule Alteration: Missense mutation; p.Q61L (c.182A>T)
• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: T24 cells; Bladder; Homo sapiens (Human); CVCL_0554
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: RL952 cells; Endometrium; Homo sapiens (Human); CVCL_0505
• In Vitro Model: NCI-H1915 cells; Lung; Homo sapiens (Human); CVCL_1505
• In Vitro Model: KYSE-30 cells; Esophagus; Homo sapiens (Human); CVCL_1351
• In Vitro Model: KNS62 cells; Brain; Homo sapiens (Human); CVCL_1335
• In Vitro Model: HCC78 cells; Pleural effusion; Homo sapiens (Human); CVCL_2061
• In Vitro Model: HCC44 cells; Lung; Homo sapiens (Human); CVCL_2060
• In Vitro Model: CAL-12T cells; Lung; Homo sapiens (Human); CVCL_1105
• In Vivo Model: CB17 SCID-/- mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CellTiter-Glo assay

Bladder cancer [ICD-11: 2C94]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: GTPase Hras (HRAS) [2]

• Molecule Alteration: Missense mutation; p.G12V (c.35G>T)
• Sensitive Disease: Bladder cancer [ICD-11: 2C94.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: T24 cells; Bladder; Homo sapiens (Human); CVCL_0554
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: RL952 cells; Endometrium; Homo sapiens (Human); CVCL_0505
• In Vitro Model: NCI-H1915 cells; Lung; Homo sapiens (Human); CVCL_1505
• In Vitro Model: KYSE-30 cells; Esophagus; Homo sapiens (Human); CVCL_1351
• In Vitro Model: KNS62 cells; Brain; Homo sapiens (Human); CVCL_1335
• In Vitro Model: HCC78 cells; Pleural effusion; Homo sapiens (Human); CVCL_2061
• In Vitro Model: HCC44 cells; Lung; Homo sapiens (Human); CVCL_2060
• In Vitro Model: CAL-12T cells; Lung; Homo sapiens (Human); CVCL_1105
• In Vivo Model: CB17 SCID-/- mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CellTiter-Glo assay

References

• Ref 1: BRAF Status in Personalizing Treatment Approaches for Pediatric GliomasClin Cancer Res. 2016 Nov 1;22(21):5312-5321. doi: 10.1158/1078-0432.CCR-15-1101. Epub 2016 May 23.
• Ref 2: Mutant HRAS as novel target for MEK and mTOR inhibitorsOncotarget. 2015 Dec 8;6(39):42183-96. doi: 10.18632/oncotarget.5619.