Drug Information

Drug (ID: DG01688) and It's Reported Resistant Information

• Name: Sirolimus/Trametinib
• Synonyms: Sirolimus/Trametinib
• 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

Head and neck cancer [ICD-11: 2D42]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: GTPase Hras (HRAS) [1]

• Molecule Alteration: Missense mutation; p.Q61L (c.182A>T)
• Sensitive Disease: Head and neck squamous cell carcinoma [ICD-11: 2D42.1]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: PI3K/mTOR signaling pathway; Inhibition; hsa04151
• In Vitro Model: CAL27 cells; Oral; Homo sapiens (Human); CVCL_1107
• In Vitro Model: UM-SCC-17B cells; Cervical lymph node; Homo sapiens (Human); CVCL_7725
• In Vitro Model: Detroit 562 cells; Pleural effusion; Homo sapiens (Human); CVCL_1171
• In Vivo Model: Athymic nude mouse tumor xenografts model; Mus musculus
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: Alamar blue cell viability reagent assay
• Mechanism Description: mTOR and MEK inhibition display a synergistic growth inhibitory activity in HNSCC cells genetically engineered to express activating KRAS and PIK3CA mutations. Antitumoral activity of the rapamycin and trametinib combination therapy increase in genetically engineered HNSCC cells expressing activating RAS or PIK3CA mutations

Key Molecule: PI3-kinase alpha (PIK3CA) [1]

• Molecule Alteration: Missense mutation; p.H1047R (c.3140A>G)
• Sensitive Disease: Head and neck squamous cell carcinoma [ICD-11: 2D42.1]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: PI3K/mTOR signaling pathway; Inhibition; hsa04151
• In Vitro Model: CAL27 cells; Oral; Homo sapiens (Human); CVCL_1107
• In Vitro Model: UM-SCC-17B cells; Cervical lymph node; Homo sapiens (Human); CVCL_7725
• In Vitro Model: Detroit 562 cells; Pleural effusion; Homo sapiens (Human); CVCL_1171
• In Vivo Model: Athymic nude mouse tumor xenografts model; Mus musculus
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: Alamar blue cell viability reagent assay
• Mechanism Description: mTOR and MEK inhibition display a synergistic growth inhibitory activity in HNSCC cells genetically engineered to express activating KRAS and PIK3CA mutations. Antitumoral activity of the rapamycin and trametinib combination therapy increase in genetically engineered HNSCC cells expressing activating RAS or PIK3CA mutations

References

• Ref 1: A synthetic-lethality RNAi screen reveals an ERK-mTOR co-targeting pro-apoptotic switch in PIK3CA+ oral cancersOncotarget. 2016 Mar 8;7(10):10696-709. doi: 10.18632/oncotarget.7372.