Disease Information

General Information of the Disease (ID: DIS00075)
Name
Liver cancer
ICD
ICD-11: 2C12
Resistance Map
Type(s) of Resistant Mechanism of This Disease with Structure Alteration
  ADTT: Aberration of the Drug's Therapeutic Target
Drug Resistance Data Categorized by Drug
Approved Drug(s)
2 drug(s) in total
Click to Show/Hide the Full List of Drugs
Dabrafenib/Trametinib
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [1]
Sensitive Disease Cholangiocarcinoma [ICD-11: 2C12.0]
Sensitive Drug Dabrafenib/Trametinib
 Drug Info 
Molecule Alteration Missense mutation
p.V600E (c.1799T>A)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 2.55  Å
PDB: 4E26
Mutant Type Structure Method: X-ray diffraction Resolution: 3.20  Å
PDB: 4G9R
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.53
TM score: 0.95765
Amino acid change:
V600E
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
420
|
M
M
D
D
R
R
G
G
S
S
H
H
H
H
H
H
H
H
H
H
430
|
H
H
G
G
S
S
E
E
D
D
R
R
N
N
R
R
M
M
K
K
440
|
T
T
L
L
G
G
R
R
R
R
D
D
S
S
S
S
D
D
D
D
450
|
W
W
E
E
I
I
P
P
D
D
G
G
Q
Q
I
I
T
T
V
V
460
|
G
G
Q
Q
R
R
I
I
G
G
S
S
G
G
S
S
F
F
G
G
470
|
T
T
V
V
Y
Y
K
K
G
G
K
K
W
W
H
H
G
G
D
D
480
|
V
V
A
A
V
V
K
K
M
M
L
L
N
N
V
V
T
T
A
A
490
|
P
P
T
T
P
P
Q
Q
Q
Q
L
L
Q
Q
A
A
F
F
K
K
500
|
N
N
E
E
V
V
G
G
V
V
L
L
R
R
K
K
T
T
R
R
510
|
H
H
V
V
N
N
I
I
L
L
L
L
F
F
M
M
G
G
Y
Y
520
|
S
S
T
T
K
K
P
P
Q
Q
L
L
A
A
I
I
V
V
T
T
530
|
Q
Q
W
W
C
C
E
E
G
G
S
S
S
S
L
L
Y
Y
H
H
540
|
H
H
L
L
H
H
I
I
I
I
E
E
T
T
K
K
F
F
E
E
550
|
M
M
I
I
K
K
L
L
I
I
D
D
I
I
A
A
R
R
Q
Q
560
|
T
T
A
A
Q
Q
G
G
M
M
D
D
Y
Y
L
L
H
H
A
A
570
|
K
K
S
S
I
I
I
I
H
H
R
R
D
D
L
L
K
K
S
S
580
|
N
N
N
N
I
I
F
F
L
L
H
H
E
E
D
D
L
L
T
T
590
|
V
V
K
K
I
I
G
G
D
D
F
F
G
G
L
L
A
A
T
T
600
|
V
E
K
K
S
S
R
R
W
W
S
S
G
G
S
S
H
H
Q
Q
610
|
F
F
E
E
Q
Q
L
L
S
S
G
G
S
S
I
I
L
L
W
W
620
|
M
M
A
A
P
P
E
E
V
V
I
I
R
R
M
M
Q
Q
D
D
630
|
K
K
N
N
P
P
Y
Y
S
S
F
F
Q
Q
S
S
D
D
V
V
640
|
Y
Y
A
A
F
F
G
G
I
I
V
V
L
L
Y
Y
E
E
L
L
650
|
M
M
T
T
G
G
Q
Q
L
L
P
P
Y
Y
S
S
N
N
I
I
660
|
N
N
N
N
R
R
D
D
Q
Q
I
I
I
I
F
F
M
M
V
V
670
|
G
G
R
R
G
G
Y
Y
L
L
S
S
P
P
D
D
L
L
S
S
680
|
K
K
V
V
R
R
S
S
N
N
C
C
P
P
K
K
A
A
M
M
690
|
K
K
R
R
L
L
M
M
A
A
E
E
C
C
L
L
K
K
K
K
700
|
K
K
R
R
D
D
E
E
R
R
P
P
L
L
F
F
P
P
Q
Q
710
|
I
I
L
L
A
A
S
S
I
I
E
E
L
L
L
L
A
A
R
R
720
|
S
S
L
L
P
P
K
K
I
I
H
H
R
R
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Erdafitinib
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Fibroblast growth factor receptor 4 (FGFR4) [2]
Resistant Disease Intrahepatic cholangiocarcinoma [ICD-11: 2C12.1]
Resistant Drug Erdafitinib
 Drug Info 
Molecule Alteration Missense mutation
p.V550L
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 2.35  Å
PDB: 5JKG
Mutant Type Structure Method: X-ray diffraction Resolution: 1.68  Å
PDB: 4QQJ
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.26
TM score: 0.94767
Amino acid change:
V550L
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
-
M
-
G
-
S
-
S
-
H
-
H
-
H
-
H
-
H
440
|
-
H
-
S
-
Q
G
D
P
P
L
L
L
L
A
A
G
G
L
L
450
|
V
V
S
S
L
L
D
D
L
L
P
P
L
L
D
D
P
P
L
L
460
|
W
W
E
E
F
F
P
P
R
R
D
D
R
R
L
L
V
V
L
L
470
|
G
G
K
K
P
P
L
L
G
G
E
E
G
G
A
A
F
F
G
G
480
|
Q
Q
V
V
V
V
R
R
A
A
E
E
A
A
F
F
G
G
M
M
490
|
D
D
P
P
A
A
R
R
P
P
D
D
Q
Q
A
A
S
S
T
T
500
|
V
V
A
A
V
V
K
K
M
M
L
L
K
K
D
D
N
N
A
A
510
|
S
S
D
D
K
K
D
D
L
L
A
A
D
D
L
L
V
V
S
S
520
|
E
E
M
M
E
E
V
V
M
M
K
K
L
L
I
I
G
G
R
R
530
|
H
H
K
K
N
N
I
I
I
I
N
N
L
L
L
L
G
G
V
V
540
|
C
C
T
T
Q
Q
E
E
G
G
P
P
L
L
Y
Y
V
V
I
I
550
|
V
L
E
E
C
C
A
A
A
A
K
K
G
G
N
N
L
L
R
R
560
|
E
E
F
F
L
L
R
R
A
A
R
R
R
R
P
P
P
P
G
G
570
|
P
P
D
D
L
L
S
S
P
P
D
D
G
G
P
P
R
R
S
S
580
|
S
S
E
E
G
G
P
P
L
L
S
S
F
F
P
P
V
V
L
L
590
|
V
V
S
S
C
C
A
A
Y
Y
Q
Q
V
V
A
A
R
R
G
G
600
|
M
M
Q
Q
Y
Y
L
L
E
E
S
S
R
R
K
K
C
C
I
I
610
|
H
H
R
R
D
D
L
L
A
A
A
A
R
R
N
N
V
V
L
L
620
|
V
V
T
T
E
E
D
D
N
N
V
V
M
M
K
K
I
I
A
A
630
|
D
D
F
F
G
G
L
L
A
A
R
R
G
G
V
V
H
H
H
H
640
|
I
I
D
D
Y
Y
Y
Y
K
K
K
K
T
T
S
S
N
N
G
G
650
|
R
R
L
L
P
P
V
V
K
K
W
W
M
M
A
A
P
P
E
E
660
|
A
A
L
L
F
F
D
D
R
E
V
V
Y
Y
T
T
H
H
Q
Q
670
|
S
S
D
D
V
V
W
W
S
S
F
F
G
G
I
I
L
L
L
L
680
|
W
W
E
E
I
I
F
F
T
T
L
L
G
G
G
G
S
S
P
P
690
|
Y
Y
P
P
G
G
I
I
P
P
V
V
E
E
E
E
L
L
F
F
700
|
S
S
L
L
L
L
R
R
E
E
G
G
H
H
R
R
M
M
D
D
710
|
R
R
P
P
P
P
H
H
C
C
P
P
P
P
E
E
L
L
Y
Y
720
|
G
G
L
L
M
M
R
R
E
E
C
C
W
W
H
H
A
A
A
A
730
|
P
P
S
S
Q
Q
R
R
P
P
T
T
F
F
K
K
Q
Q
L
L
740
|
V
V
E
E
A
A
L
L
D
D
K
K
V
V
L
L
L
L
A
A
750
|
V
V
S
S
E
E
E
E
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Mechanism Description The mutations V550L and V550E in the FGFR4 kinase domain have been demonstrated to confer clinical resistance to erdafitinib in rhabdomyosarcoma, while V550M is associated with erdafitinib resistance in breast cancer.
Key Molecule: Fibroblast growth factor receptor 4 (FGFR4) [2]
Resistant Disease Intrahepatic cholangiocarcinoma [ICD-11: 2C12.1]
Resistant Drug Erdafitinib
 Drug Info 
Molecule Alteration Missense mutation
p.V550L
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 2.35  Å
PDB: 5JKG
Mutant Type Structure Method: X-ray diffraction Resolution: 1.68  Å
PDB: 4QQJ
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.26
TM score: 0.94767
Amino acid change:
V550L
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
-
M
-
G
-
S
-
S
-
H
-
H
-
H
-
H
-
H
440
|
-
H
-
S
-
Q
G
D
P
P
L
L
L
L
A
A
G
G
L
L
450
|
V
V
S
S
L
L
D
D
L
L
P
P
L
L
D
D
P
P
L
L
460
|
W
W
E
E
F
F
P
P
R
R
D
D
R
R
L
L
V
V
L
L
470
|
G
G
K
K
P
P
L
L
G
G
E
E
G
G
A
A
F
F
G
G
480
|
Q
Q
V
V
V
V
R
R
A
A
E
E
A
A
F
F
G
G
M
M
490
|
D
D
P
P
A
A
R
R
P
P
D
D
Q
Q
A
A
S
S
T
T
500
|
V
V
A
A
V
V
K
K
M
M
L
L
K
K
D
D
N
N
A
A
510
|
S
S
D
D
K
K
D
D
L
L
A
A
D
D
L
L
V
V
S
S
520
|
E
E
M
M
E
E
V
V
M
M
K
K
L
L
I
I
G
G
R
R
530
|
H
H
K
K
N
N
I
I
I
I
N
N
L
L
L
L
G
G
V
V
540
|
C
C
T
T
Q
Q
E
E
G
G
P
P
L
L
Y
Y
V
V
I
I
550
|
V
L
E
E
C
C
A
A
A
A
K
K
G
G
N
N
L
L
R
R
560
|
E
E
F
F
L
L
R
R
A
A
R
R
R
R
P
P
P
P
G
G
570
|
P
P
D
D
L
L
S
S
P
P
D
D
G
G
P
P
R
R
S
S
580
|
S
S
E
E
G
G
P
P
L
L
S
S
F
F
P
P
V
V
L
L
590
|
V
V
S
S
C
C
A
A
Y
Y
Q
Q
V
V
A
A
R
R
G
G
600
|
M
M
Q
Q
Y
Y
L
L
E
E
S
S
R
R
K
K
C
C
I
I
610
|
H
H
R
R
D
D
L
L
A
A
A
A
R
R
N
N
V
V
L
L
620
|
V
V
T
T
E
E
D
D
N
N
V
V
M
M
K
K
I
I
A
A
630
|
D
D
F
F
G
G
L
L
A
A
R
R
G
G
V
V
H
H
H
H
640
|
I
I
D
D
Y
Y
Y
Y
K
K
K
K
T
T
S
S
N
N
G
G
650
|
R
R
L
L
P
P
V
V
K
K
W
W
M
M
A
A
P
P
E
E
660
|
A
A
L
L
F
F
D
D
R
E
V
V
Y
Y
T
T
H
H
Q
Q
670
|
S
S
D
D
V
V
W
W
S
S
F
F
G
G
I
I
L
L
L
L
680
|
W
W
E
E
I
I
F
F
T
T
L
L
G
G
G
G
S
S
P
P
690
|
Y
Y
P
P
G
G
I
I
P
P
V
V
E
E
E
E
L
L
F
F
700
|
S
S
L
L
L
L
R
R
E
E
G
G
H
H
R
R
M
M
D
D
710
|
R
R
P
P
P
P
H
H
C
C
P
P
P
P
E
E
L
L
Y
Y
720
|
G
G
L
L
M
M
R
R
E
E
C
C
W
W
H
H
A
A
A
A
730
|
P
P
S
S
Q
Q
R
R
P
P
T
T
F
F
K
K
Q
Q
L
L
740
|
V
V
E
E
A
A
L
L
D
D
K
K
V
V
L
L
L
L
A
A
750
|
V
V
S
S
E
E
E
E
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Mechanism Description The mutations V550L and V550E in the FGFR4 kinase domain have been demonstrated to confer clinical resistance to erdafitinib in rhabdomyosarcoma, while V550M is associated with erdafitinib resistance in breast cancer.
Preclinical Drug(s)
1 drug(s) in total
Click to Show/Hide the Full List of Drugs
CP-31398
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Cellular tumor antigen p53 (TP53) [3]
Sensitive Disease Cholangiocarcinoma [ICD-11: 2C12.0]
Sensitive Drug CP-31398
 Drug Info 
Molecule Alteration Missense mutation
p.Y220C (c.659A>G)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 2.05  Å
PDB: 2OCJ
Mutant Type Structure Method: X-ray diffraction Resolution: 1.24  Å
PDB: 6GGC
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.54
TM score: 0.9897
Amino acid change:
Y220C
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
S
S
S
S
S
S
V
V
P
P
S
S
100
|
Q
Q
K
K
T
T
Y
Y
Q
Q
G
G
S
S
Y
Y
G
G
F
F
110
|
R
R
L
L
G
G
F
F
L
L
H
H
S
S
G
G
T
T
A
A
120
|
K
K
S
S
V
V
T
T
C
C
T
T
Y
Y
S
S
P
P
A
A
130
|
L
L
N
N
K
K
M
L
F
F
C
C
Q
Q
L
L
A
A
K
K
140
|
T
T
C
C
P
P
V
V
Q
Q
L
L
W
W
V
V
D
D
S
S
150
|
T
T
P
P
P
P
P
P
G
G
T
T
R
R
V
V
R
R
A
A
160
|
M
M
A
A
I
I
Y
Y
K
K
Q
Q
S
S
Q
Q
H
H
M
M
170
|
T
T
E
E
V
V
V
V
R
R
R
R
C
C
P
P
H
H
H
H
180
|
E
E
R
R
C
C
S
S
D
D
S
S
D
D
G
G
L
L
A
A
190
|
P
P
P
P
Q
Q
H
H
L
L
I
I
R
R
V
V
E
E
G
G
200
|
N
N
L
L
R
R
V
A
E
E
Y
Y
L
L
D
D
D
D
R
R
210
|
N
N
T
T
F
F
R
R
H
H
S
S
V
V
V
V
V
V
P
P
220
|
Y
C
E
E
P
P
P
P
E
E
V
V
G
G
S
S
D
D
C
C
230
|
T
T
T
T
I
I
H
H
Y
Y
N
N
Y
Y
M
M
C
C
N
Y
240
|
S
S
S
S
C
C
M
M
G
G
G
G
M
M
N
N
R
R
R
R
250
|
P
P
I
I
L
L
T
T
I
I
I
I
T
T
L
L
E
E
D
D
260
|
S
S
S
S
G
G
N
N
L
L
L
L
G
G
R
R
N
D
S
S
270
|
F
F
E
E
V
V
R
R
V
V
C
C
A
A
C
C
P
P
G
G
280
|
R
R
D
D
R
R
R
R
T
T
E
E
E
E
E
E
N
N
L
L
290
|
R
R
K
K
K
K
G
G
E
E
P
P
H
H
H
H
E
E
L
L
300
|
P
P
P
P
G
G
S
S
T
T
K
K
R
R
A
A
L
L
P
P
310
|
N
N
N
N
T
T
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HepG2 cells Liver Homo sapiens (Human) CVCL_0027
Experiment for
Molecule Alteration		 qRT-PCR
Key Molecule: Cellular tumor antigen p53 (TP53) [3]
Sensitive Disease Cholangiocarcinoma [ICD-11: 2C12.0]
Sensitive Drug CP-31398
 Drug Info 
Molecule Alteration Missense mutation
p.R249S (c.747G>C)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.92  Å
PDB: 4QO1
Mutant Type Structure Method: X-ray diffraction Resolution: 1.90  Å
PDB: 2BIO
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.01
TM score: 0.95973
Amino acid change:
R249S
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
P
-
L
-
S
S
S
S
S
S
V
V
P
P
S
S
100
|
Q
Q
K
K
T
T
Y
Y
Q
Q
G
G
S
S
Y
Y
G
G
F
F
110
|
R
R
L
L
G
G
F
F
L
L
H
H
S
S
G
G
T
T
A
A
120
|
K
K
S
S
V
V
T
T
C
C
T
T
Y
Y
S
S
P
P
A
A
130
|
L
L
N
N
K
K
M
L
F
F
C
C
Q
Q
L
L
A
A
K
K
140
|
T
T
C
C
P
P
V
V
Q
Q
L
L
W
W
V
V
D
D
S
S
150
|
T
T
P
P
P
P
P
P
G
G
T
T
R
R
V
V
R
R
A
A
160
|
M
M
A
A
I
I
Y
Y
K
K
Q
Q
S
S
Q
Q
H
H
M
M
170
|
T
T
E
E
V
V
V
V
R
R
R
R
C
C
P
P
H
H
H
H
180
|
E
E
R
R
C
C
S
S
D
D
S
S
D
D
G
G
L
L
A
A
190
|
P
P
P
P
Q
Q
H
H
L
L
I
I
R
R
V
V
E
E
G
G
200
|
N
N
L
L
R
R
V
A
E
E
Y
Y
L
L
D
D
D
D
R
R
210
|
N
N
T
T
F
F
R
R
H
H
S
S
V
V
V
V
V
V
P
P
220
|
Y
Y
E
E
P
P
P
P
E
E
V
V
G
G
S
S
D
D
C
C
230
|
T
T
T
T
I
I
H
H
Y
Y
N
N
Y
Y
M
M
C
C
N
Y
240
|
S
S
S
S
C
C
M
M
G
G
G
G
M
M
N
N
R
R
R
S
250
|
P
P
I
I
L
L
T
T
I
I
I
I
T
T
L
L
E
E
D
D
260
|
S
S
S
S
G
G
N
N
L
L
L
L
G
G
R
R
N
D
S
S
270
|
F
F
E
E
V
V
R
R
V
V
C
C
A
A
C
C
P
P
G
G
280
|
R
R
D
D
R
R
R
R
T
T
E
E
E
E
E
E
N
N
L
L
290
|
R
R
K
K
K
K
G
G
E
E
P
P
H
H
H
H
E
E
L
L
300
|
P
P
P
P
G
G
S
S
T
T
K
K
R
R
A
A
L
L
P
P
310
|
N
N
N
N
T
T
H
-
H
-
H
-
H
-
H
-
H
-
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HepG2 cells Liver Homo sapiens (Human) CVCL_0027
Experiment for
Molecule Alteration		 qRT-PCR
References
Ref 1 Combined dabrafenib and trametinib treatment in a case of chemotherapy-refractory extrahepatic BRAF V600E mutant cholangiocarcinoma: dramatic clinical and radiological response with a confusing synchronic new liver lesionJ Gastrointest Oncol. 2017 Apr;8(2):E32-E38. doi: 10.21037/jgo.2017.01.06.
Ref 2 Fibroblast growth factor receptors in cancer: genetic alterations, diagnostics, therapeutic targets and mechanisms of resistance .Br J Cancer. 2021 Mar;124(5):880-892. doi: 10.1038/s41416-020-01157-0. Epub 2020 Dec 3. 10.1038/s41416-020-01157-0
Ref 3 CP-31398 inhibits the growth of p53-mutated liver cancer cells in vitro and in vivoTumour Biol. 2016 Jan;37(1):807-15. doi: 10.1007/s13277-015-3857-5. Epub 2015 Aug 7.

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