Disease Information

General Information of the Disease (ID: DIS00207)

• Name: Merkel cell carcinoma
• ICD: ICD-11: 2C34

Type(s) of Resistant Mechanism of This Disease

  ADTT: Aberration of the Drug's Therapeutic Target

  IDUE: Irregularity in Drug Uptake and Drug Efflux

Drug Resistance Data Categorized by Drug

Approved Drug(s) 3 drug(s) in total

Carboplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: ATP-binding cassette sub-family B5 (ABCB5) [1]

• Resistant Disease: Merkel cell carcinoma [ICD-11: 2C34.0]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Carboplatin
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: MKL-2 cells; Peripheral blood; Homo sapiens (Human); CVCL_D027
• In Vitro Model: WaGa cells; Ascites; Homo sapiens (Human); CVCL_E998
• In Vitro Model: MKL-1 cells; Liver; Homo sapiens (Human); CVCL_2600
• In Vitro Model: MS-1 cells; Lung; Homo sapiens (Human); CVCL_IQ55
• In Vivo Model: NSG mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR; Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: These findings in patient specimens were consistent with the possibility that ABCB5+ MCC cells are preferentially resistant to treatment with the first-line chemotherapeutic agents, carboplatin and etoposide.

Key Molecule: ATP-binding cassette sub-family B5 (ABCB5) [1]

• Resistant Disease: Merkel cell carcinoma [ICD-11: 2C34.0]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Carboplatin
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: MKL-2 cells; Peripheral blood; Homo sapiens (Human); CVCL_D027
• In Vitro Model: WaGa cells; Ascites; Homo sapiens (Human); CVCL_E998
• In Vitro Model: MKL-1 cells; Liver; Homo sapiens (Human); CVCL_2600
• In Vitro Model: MS-1 cells; Lung; Homo sapiens (Human); CVCL_IQ55
• In Vivo Model: NSG mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR; Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: These findings in patient specimens were consistent with the possibility that ABCB5+ MCC cells are preferentially resistant to treatment with the first-line chemotherapeutic agents, carboplatin and etoposide.

Etoposide

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: ATP-binding cassette sub-family B5 (ABCB5) [1]

• Resistant Disease: Merkel cell carcinoma [ICD-11: 2C34.0]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Etoposide
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: MKL-2 cells; Peripheral blood; Homo sapiens (Human); CVCL_D027
• In Vitro Model: WaGa cells; Ascites; Homo sapiens (Human); CVCL_E998
• In Vitro Model: MKL-1 cells; Liver; Homo sapiens (Human); CVCL_2600
• In Vitro Model: MS-1 cells; Lung; Homo sapiens (Human); CVCL_IQ55
• In Vivo Model: NSG mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR; Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: These findings in patient specimens were consistent with the possibility that ABCB5+ MCC cells are preferentially resistant to treatment with the first-line chemotherapeutic agents, carboplatin and etoposide.

Key Molecule: ATP-binding cassette sub-family B5 (ABCB5) [1]

• Resistant Disease: Merkel cell carcinoma [ICD-11: 2C34.0]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Etoposide
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: MKL-2 cells; Peripheral blood; Homo sapiens (Human); CVCL_D027
• In Vitro Model: WaGa cells; Ascites; Homo sapiens (Human); CVCL_E998
• In Vitro Model: MKL-1 cells; Liver; Homo sapiens (Human); CVCL_2600
• In Vitro Model: MS-1 cells; Lung; Homo sapiens (Human); CVCL_IQ55
• In Vivo Model: NSG mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR; Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: These findings in patient specimens were consistent with the possibility that ABCB5+ MCC cells are preferentially resistant to treatment with the first-line chemotherapeutic agents, carboplatin and etoposide.

Idelalisib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: PI3-kinase alpha (PIK3CA) [2]

• Sensitive Disease: Merkel cell carcinoma [ICD-11: 2C34.0]
• Molecule Alteration: Missense mutation; p.P471L (c.1412C>T)
• Sensitive Drug: Idelalisib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Skin; .
• Experiment for Molecule Alteration: Real-time PCR

References

• Ref 1: ABCB5-Targeted Chemoresistance Reversal Inhibits Merkel Cell Carcinoma Growth .J Invest Dermatol. 2016 Apr;136(4):838-846. doi: 10.1016/j.jid.2015.12.038. Epub 2016 Jan 29. 10.1016/j.jid.2015.12.038
• Ref 2: Response to Idelalisib in a Patient with Stage IV Merkel-Cell CarcinomaN Engl J Med. 2015 Oct 15;373(16):1580-2. doi: 10.1056/NEJMc1507446.