Disease Information

General Information of the Disease (ID: DIS00214)
Name
Neuroendocrine carcinoma
ICD
ICD-11: 2D4Y
Resistance Map
Type(s) of Resistant Mechanism of This Disease
  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
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [1]
Sensitive Disease Metastatic neuroendocrine carcinoma [ICD-11: 2D4Y.0]
Sensitive Drug Dabrafenib/Trametinib
 Drug Info 
Molecule Alteration Missense mutation
p.V600E (c.1406G>C)
 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
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430
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E
E
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R
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K
440
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D
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480
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490
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500
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510
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520
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530
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540
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550
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560
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570
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580
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590
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600
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E
K
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610
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620
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630
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640
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Y
Y
A
A
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F
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L
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L
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650
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T
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G
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L
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N
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I
660
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N
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D
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670
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680
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V
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C
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A
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690
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C
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700
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710
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I
I
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A
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L
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720
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P
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Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [1]
Sensitive Disease Metastatic neuroendocrine carcinoma [ICD-11: 2D4Y.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
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M
M
D
D
R
R
G
G
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H
H
H
H
H
H
H
H
430
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H
H
G
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E
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R
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K
440
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470
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480
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540
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560
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590
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610
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F
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620
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630
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640
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650
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660
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R
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D
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I
I
I
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F
M
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V
V
670
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G
G
R
R
G
G
Y
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L
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P
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D
D
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680
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690
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K
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R
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700
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K
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E
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710
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I
I
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A
A
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L
L
L
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A
R
R
720
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S
S
L
L
P
P
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I
I
H
H
R
R
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Nivolumab
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: Fibroblast growth factor receptor 3 (FGFR3) [2]
Resistant Disease Primary pulmonary lymphoepithelioma-like carcinoma [ICD-11: 2D4Y.Z]
Resistant Drug Nivolumab
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model KB-3-1 cells Lung Homo sapiens (Human) CVCL_2088
Mechanism Description Pulmonary LELC with FGFR3 gene amplification may not respond well to nivolumab monotherapy. The combination of anlotinib and nivolumab can reverse the resistance to nivolumab in pulmonary LELC with FGFR3 gene amplification.
Investigative Drug(s)
1 drug(s) in total
Click to Show/Hide the Full List of Drugs
Trametinib/Vemurafenib
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [1]
Sensitive Disease Metastatic neuroendocrine carcinoma [ICD-11: 2D4Y.0]
Sensitive Drug Trametinib/Vemurafenib
 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
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M
M
D
D
R
R
G
G
S
S
H
H
H
H
H
H
H
H
H
H
430
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H
H
G
G
S
S
E
E
D
D
R
R
N
N
R
R
M
M
K
K
440
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T
T
L
L
G
G
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R
R
R
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D
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W
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G
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470
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480
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A
490
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T
P
P
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500
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N
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E
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520
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580
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610
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F
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D
630
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N
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Y
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V
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640
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I
660
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N
N
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D
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680
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690
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Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
References
Ref 1 BRAFV600E Mutations in High-Grade Colorectal Neuroendocrine Tumors May Predict Responsiveness to BRAF-MEK Combination TherapyCancer Discov. 2016 Jun;6(6):594-600. doi: 10.1158/2159-8290.CD-15-1192. Epub 2016 Apr 5.
Ref 2 Case Report: Anlotinib Reverses Nivolumab Resistance in Advanced Primary Pulmonary Lymphoepithelioma-Like Carcinoma With FGFR3 Gene Amplification .Front Oncol. 2021 Oct 8;11:749682. doi: 10.3389/fonc.2021.749682. eCollection 2021. 10.3389/fonc.2021.749682

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