Disease Information

General Information of the Disease (ID: DIS00221)
Name
Salivary gland carcinoma
ICD
ICD-11: 2E60
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)
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 Salivary gland adenoid cystic carcinoma [ICD-11: 2E60.0]
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
In Vitro Model Human laryngeal cells isolates N.A.
Experiment for
Molecule Alteration		 ctDNA sequencing assay
Fluorouracil
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Prominin-1 (PROM1) [2]
Resistant Disease Salivary gland adenoid cystic carcinoma [ICD-11: 2E60.0]
Resistant Drug Fluorouracil
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation MET/PI3K/AKT/mTOR signaling pathway Activation hsa04150
Cell migration Activation hsa04670
Cell invasion Activation hsa05200
In Vitro Model KOA-1 cells Skin Homo sapiens (Human) CVCL_L997
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CCK-8 assay
Mechanism Description CD133 activates the PI3K/AKT, AKT/Wnt and other signaling pathways and affects the behavior of CD133+ cells, thereby playing a major role in cancer therapy. In addition, CD133 is also involved in the regulation of tumor resistance. Long-term chemotherapy leads to a significant increase in CD133 expression. Targeting CD133 can reverse drug resistance in colorectal cancer via the AKT/NF-kappa-B/multidrug resistance protein (MDR)1 pathway.
Investigative Drug(s)
1 drug(s) in total
Click to Show/Hide the Full List of Drugs
Pingyangmycin
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Prominin-1 (PROM1) [2]
Resistant Disease Salivary gland adenoid cystic carcinoma [ICD-11: 2E60.0]
Resistant Drug Pingyangmycin
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation MET/PI3K/AKT/mTOR signaling pathway Activation hsa04150
Cell migration Activation hsa04670
Cell invasion Activation hsa05200
In Vitro Model KOA-1 cells Skin Homo sapiens (Human) CVCL_L997
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CCK-8 assay
Mechanism Description CD133 activates the PI3K/AKT, AKT/Wnt and other signaling pathways and affects the behavior of CD133+ cells, thereby playing a major role in cancer therapy. In addition, CD133 is also involved in the regulation of tumor resistance. Long-term chemotherapy leads to a significant increase in CD133 expression. Targeting CD133 can reverse drug resistance in colorectal cancer via the AKT/NF-kappa-B/multidrug resistance protein (MDR)1 pathway.
References
Ref 1 First-Line Treatment of Widely Metastatic BRAF-Mutated Salivary Duct Carcinoma With Combined BRAF and MEK InhibitionJ Natl Compr Canc Netw. 2018 Oct;16(10):1166-1170. doi: 10.6004/jnccn.2018.7056.
Ref 2 Effects of CD133 expression on chemotherapy and drug sensitivity of adenoid cystic carcinoma .Mol Med Rep. 2022 Jan;25(1):18. doi: 10.3892/mmr.2021.12534. Epub 2021 Nov 18. 10.3892/mmr.2021.12534

If you find any error in data or bug in web service, please kindly report it to Dr. Sun and Dr. Yu.