Disease Information

General Information of the Disease (ID: DIS00201)
Name
Leiomyosarcoma
ICD
ICD-11: 2B58
Resistance Map
Type(s) of Resistant Mechanism of This Disease
  ADTT: Aberration of the Drug's Therapeutic Target
  UAPP: Unusual Activation of Pro-survival Pathway
Drug Resistance Data Categorized by Drug
Approved Drug(s)
1 drug(s) in total
Click to Show/Hide the Full List of Drugs
Doxorubicin
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Nanog homeobox (NANOG) [1]
Resistant Disease Leiomyosarcoma [ICD-11: 2B58.0]
Resistant Drug Doxorubicin
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Spheroid formation Activation hsa04140
Cell colony Activation hsa05200
Cell migration Activation hsa04670
In Vitro Model SK-UT-1 cells Uterus Homo sapiens (Human) CVCL_0533
In Vivo Model BALB/c-nu female mice Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CCK-8 assay; Flow cytometry assay; Transwell migration and invasion assay
Mechanism Description The expression levels of CSC-related markers in CD133+ subpopulation derived from SK-UT-1 cells, Western blotting was employed to detect the expression levels of CD44, ALDH1, BMI1, and Nanog. Expectedly, researchers found that CD133+subpopulation had higher expression levels of CD44, ALDH1, BMI1, and Nanog compared with those of CD133 subpopulation. Collectively, the above-mentioned results suggested that CD133+ subpopulation derived from SK-UT-1 cells possessed capabilities of resistance to apoptosis after treatment with DXR, as well as stemness feature of cancer stem-like cells.
Key Molecule: Extracellular matrix receptor III (CD44) [1]
Resistant Disease Leiomyosarcoma [ICD-11: 2B58.0]
Resistant Drug Doxorubicin
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Spheroid formation Activation hsa04140
Cell colony Activation hsa05200
Cell migration Activation hsa04670
In Vitro Model SK-UT-1 cells Uterus Homo sapiens (Human) CVCL_0533
In Vivo Model BALB/c-nu female mice Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CCK-8 assay; Flow cytometry assay; Transwell migration and invasion assay
Mechanism Description The expression levels of CSC-related markers in CD133+ subpopulation derived from SK-UT-1 cells, Western blotting was employed to detect the expression levels of CD44, ALDH1, BMI1, and Nanog. Expectedly, researchers found that CD133+subpopulation had higher expression levels of CD44, ALDH1, BMI1, and Nanog compared with those of CD133 subpopulation. Collectively, the above-mentioned results suggested that CD133+ subpopulation derived from SK-UT-1 cells possessed capabilities of resistance to apoptosis after treatment with DXR, as well as stemness feature of cancer stem-like cells.
Key Molecule: Polycomb complex protein BMI-1 (BMI1) [1]
Resistant Disease Leiomyosarcoma [ICD-11: 2B58.0]
Resistant Drug Doxorubicin
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Spheroid formation Activation hsa04140
Cell colony Activation hsa05200
Cell migration Activation hsa04670
In Vitro Model SK-UT-1 cells Uterus Homo sapiens (Human) CVCL_0533
In Vivo Model BALB/c-nu female mice Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CCK-8 assay; Flow cytometry assay; Transwell migration and invasion assay
Mechanism Description The expression levels of CSC-related markers in CD133+ subpopulation derived from SK-UT-1 cells, Western blotting was employed to detect the expression levels of CD44, ALDH1, BMI1, and Nanog. Expectedly, researchers found that CD133+subpopulation had higher expression levels of CD44, ALDH1, BMI1, and Nanog compared with those of CD133 subpopulation. Collectively, the above-mentioned results suggested that CD133+ subpopulation derived from SK-UT-1 cells possessed capabilities of resistance to apoptosis after treatment with DXR, as well as stemness feature of cancer stem-like cells.
Key Molecule: Nanog homeobox (NANOG) [1]
Resistant Disease Leiomyosarcoma [ICD-11: 2B58.0]
Resistant Drug Doxorubicin
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Spheroid formation Activation hsa04140
Cell colony Activation hsa05200
Cell migration Activation hsa04670
In Vitro Model SK-UT-1 cells Uterus Homo sapiens (Human) CVCL_0533
In Vivo Model BALB/c-nu female mice Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CCK-8 assay; Flow cytometry assay; Transwell migration and invasion assay
Mechanism Description The expression levels of CSC-related markers in CD133+ subpopulation derived from SK-UT-1 cells, Western blotting was employed to detect the expression levels of CD44, ALDH1, BMI1, and Nanog. Expectedly, researchers found that CD133+subpopulation had higher expression levels of CD44, ALDH1, BMI1, and Nanog compared with those of CD133 subpopulation. Collectively, the above-mentioned results suggested that CD133+ subpopulation derived from SK-UT-1 cells possessed capabilities of resistance to apoptosis after treatment with DXR, as well as stemness feature of cancer stem-like cells.
Key Molecule: Extracellular matrix receptor III (CD44) [1]
Resistant Disease Leiomyosarcoma [ICD-11: 2B58.0]
Resistant Drug Doxorubicin
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Spheroid formation Activation hsa04140
Cell colony Activation hsa05200
Cell migration Activation hsa04670
In Vitro Model SK-UT-1 cells Uterus Homo sapiens (Human) CVCL_0533
In Vivo Model BALB/c-nu female mice Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CCK-8 assay; Flow cytometry assay; Transwell migration and invasion assay
Mechanism Description The expression levels of CSC-related markers in CD133+ subpopulation derived from SK-UT-1 cells, Western blotting was employed to detect the expression levels of CD44, ALDH1, BMI1, and Nanog. Expectedly, researchers found that CD133+subpopulation had higher expression levels of CD44, ALDH1, BMI1, and Nanog compared with those of CD133 subpopulation. Collectively, the above-mentioned results suggested that CD133+ subpopulation derived from SK-UT-1 cells possessed capabilities of resistance to apoptosis after treatment with DXR, as well as stemness feature of cancer stem-like cells.
Key Molecule: Polycomb complex protein BMI-1 (BMI1) [1]
Resistant Disease Leiomyosarcoma [ICD-11: 2B58.0]
Resistant Drug Doxorubicin
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Spheroid formation Activation hsa04140
Cell colony Activation hsa05200
Cell migration Activation hsa04670
In Vitro Model SK-UT-1 cells Uterus Homo sapiens (Human) CVCL_0533
In Vivo Model BALB/c-nu female mice Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CCK-8 assay; Flow cytometry assay; Transwell migration and invasion assay
Mechanism Description The expression levels of CSC-related markers in CD133+ subpopulation derived from SK-UT-1 cells, Western blotting was employed to detect the expression levels of CD44, ALDH1, BMI1, and Nanog. Expectedly, researchers found that CD133+subpopulation had higher expression levels of CD44, ALDH1, BMI1, and Nanog compared with those of CD133 subpopulation. Collectively, the above-mentioned results suggested that CD133+ subpopulation derived from SK-UT-1 cells possessed capabilities of resistance to apoptosis after treatment with DXR, as well as stemness feature of cancer stem-like cells.
Clinical Trial Drug(s)
1 drug(s) in total
Click to Show/Hide the Full List of Drugs
Capivasertib
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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: RAC-alpha serine/threonine-protein kinase (AKT1) [2]
Sensitive Disease Leiomyosarcoma [ICD-11: 2B58.0]
Sensitive Drug Capivasertib
 Drug Info 
Molecule Alteration Missense mutation
p.E17K (c.49G>A)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.65  Å
PDB: 1UNP
Mutant Type Structure Method: X-ray diffraction Resolution: 1.94  Å
PDB: 2UZR
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.26
TM score: 0.99569
Amino acid change:
E17K
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
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0
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10
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G
G
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H
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G
G
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Y
I
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20
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30
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40
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50
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L
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F
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60
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C
C
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L
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M
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70
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80
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90
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100
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110
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120
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G
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model Breast N.A.
Mechanism Description The missense mutation p.E17K (c.49G>A) in gene AKT1 cause the sensitivity of Capivasertib by aberration of the drug's therapeutic target
References
Ref 1 Identification and characterization of a subpopulation of CD133(+) cancer stem-like cells derived from SK-UT-1 cells .Cancer Cell Int. 2021 Mar 8;21(1):157. doi: 10.1186/s12935-021-01817-y. 10.1186/s12935-021-01817-y
Ref 2 Capivasertib Active against AKT1-Mutated CancersCancer Discov. 2019 Jan;9(1):OF7. doi: 10.1158/2159-8290.CD-NB2018-153. Epub 2018 Nov 14.

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