Drug Information

Drug (ID: DG00502) and It's Reported Resistant Information

• Name: TKIS

Type(s) of Resistant Mechanism of This Drug

  EADR: Epigenetic Alteration of DNA, RNA or Protein

Drug Resistance Data Categorized by Their Corresponding Diseases

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

Skin squamous cell carcinoma [ICD-11: 2C31]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: EGFR antisense RNA 1 (EGFR-AS1) [1]

• Molecule Alteration: Expression; Down-regulation
• Sensitive Disease: Squamous cell carcinoma [ICD-11: 2B6E.3]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Ligand-mediated signaling pathway; Activation; hsa04210
• In Vitro Model: HN1 cells; Tongue; Homo sapiens (Human); CVCL_8123
• In Vitro Model: HN148 cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: HN159 cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: HN177 cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: HN19 cells; Lymph node; Homo sapiens (Human); CVCL_5521
• In Vitro Model: HN43 cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: HN64 cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: NCC-HN26 cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: NCC-HN73 cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: NCC-HN90 cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: HN137 cells; N.A.; Homo sapiens (Human); N.A.
• In Vivo Model: Mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Northern blot analysis
• Experiment for Drug Resistance: CellTiter-Glo Luminescent Assay
• Mechanism Description: Long noncoding RNA EGFR-AS1 mediates epidermal growth factor receptor addiction and modulates treatment response in squamous cell carcinoma. Sensitivity could be recapitulated through EGFR-AS1 knockdown in vitro and in vivo, whereas overexpression was sufficient to induce resistance to TkIs. Increased expression of the EGFR-AS1 LncRNA results in differential splicing of EGFR isoforms A and D and consequent ligand-dependent activation of the EGFR pathway.

References

• Ref 1: Long noncoding RNA EGFR-AS1 mediates epidermal growth factor receptor addiction and modulates treatment response in squamous cell carcinoma. Nat Med. 2017 Oct;23(10):1167-1175. doi: 10.1038/nm.4401. Epub 2017 Sep 18.