Drug Information

Drug (ID: DG02145) and It's Reported Resistant Information

• Name: Erlotinib/Gemcitabine
• Synonyms: Erlotinib/Gemcitabine
• Indication:
  In total 1 Indication(s)
  . .; .; [1]

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Their Corresponding Diseases

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

Liver cancer [ICD-11: 2C12]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Oncogenic epidermal growth factor receptor (EGFR) [1]

• Sensitive Disease: Cholangiocarcinoma [ICD-11: 2C12.00]
• Molecule Alteration: phosphorylation; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: CCA-GemR cells; Bile duct; Homo sapiens (Human); N.A.
• In Vitro Model: KKU-213A-GemR cells; Bile duct; Homo sapiens (Human); N.A.
• In Vitro Model: KKU-213B-GemR cells; Bile duct; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blot assay
• Experiment for Drug Resistance: Cell cycle distribution assay; Colony formation assay
• Mechanism Description: The results demonstrated that CCA-GemR cells grow more slowly compared to their parental cell lines. Cell cycle analysis revealed an increase in KKU-213A-GemR and KKU-213B-GemR cell accumulation in the G1 phase. Moreover, cross-resistance to 5-FU and cisplatin was observed in all CCA-GemR cells. The Proteome Profiler Human Phospho-Kinase Array showed increased phosphorylation of EGFR in CCA-GemR cells. Erlotinib, a specific inhibitor of EGFR, significantly enhanced the anti-tumor activity of Gem with a synergistic effect (Combination index <1). Western blot analysis confirmed that phosphorylation of EGFR increased in cells treated with Gem, whereas the expression was significantly decreased in cells treated with either erlotinib alone or in combination with Gem.

References

• Ref 1: Targeting EGFR Activation to Overcome Gemcitabine Resistance in Cholangiocarcinoma. Anticancer Res. 2024 Dec;44(12):5393-5404.