Disease Information

General Information of the Disease (ID: DIS00207)
Name
Merkel cell carcinoma
ICD
ICD-11: 2C34
Resistance Map
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
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Carboplatin
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Irregularity in Drug Uptake and Drug Efflux (IDUE) Click to Show/Hide
Key Molecule: ATP-binding cassette sub-family B5 (ABCB5) [1]
Resistant Disease Merkel cell carcinoma [ICD-11: 2C34.0]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Drug Carboplatin
 Drug Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model MKL-2 cells Peripheral blood Homo sapiens (Human) CVCL_D027
WaGa cells Ascites Homo sapiens (Human) CVCL_E998
MKL-1 cells Liver Homo sapiens (Human) CVCL_2600
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
 Molecule Info 
Resistant Drug Carboplatin
 Drug Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model MKL-2 cells Peripheral blood Homo sapiens (Human) CVCL_D027
WaGa cells Ascites Homo sapiens (Human) CVCL_E998
MKL-1 cells Liver Homo sapiens (Human) CVCL_2600
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
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Irregularity in Drug Uptake and Drug Efflux (IDUE) Click to Show/Hide
Key Molecule: ATP-binding cassette sub-family B5 (ABCB5) [1]
Resistant Disease Merkel cell carcinoma [ICD-11: 2C34.0]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Drug Etoposide
 Drug Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model MKL-2 cells Peripheral blood Homo sapiens (Human) CVCL_D027
WaGa cells Ascites Homo sapiens (Human) CVCL_E998
MKL-1 cells Liver Homo sapiens (Human) CVCL_2600
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
 Molecule Info 
Resistant Drug Etoposide
 Drug Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model MKL-2 cells Peripheral blood Homo sapiens (Human) CVCL_D027
WaGa cells Ascites Homo sapiens (Human) CVCL_E998
MKL-1 cells Liver Homo sapiens (Human) CVCL_2600
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
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
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)
 Molecule Info 
Sensitive Drug Idelalisib
 Drug Info 
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.

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