Drug Information

Drug (ID: DG00342) and It's Reported Resistant Information
Name
Pertuzumab
Synonyms
Pertuzumab (genetical recombination); Pertuzumab (USAN/INN); Pertuzumab (genetical recombination) (JAN); Pertuzumab (ERBB2 mAb inhibitor)
    Click to Show/Hide
Indication
In total 1 Indication(s)
Breast cancer [ICD-11: 2C60]
Approved
[1]
Drug Resistance Disease(s)
Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
Breast cancer [ICD-11: 2C60]
[1]
Target Erbb2 tyrosine kinase receptor (HER2) ERBB2_HUMAN [1]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
TTD Drug ID
D0CI4E
DrugBank ID
DB06366
Type(s) of Resistant Mechanism of This Drug
  UAPP: Unusual Activation of Pro-survival Pathway
Drug Resistance Data Categorized by Their Corresponding Diseases
ICD-02: Benign/in-situ/malignant neoplasm
Click to Show/Hide the Resistance Disease of This Class
Breast cancer [ICD-11: 2C60]
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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: GTPase Hras (HRAS) [1]
Resistant Disease HER2 positive breast cancer [ICD-11: 2C60.8]
 Disease Info 
Molecule Alteration Missense mutation
p.G12S
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.24  Å
PDB: 4OBE
Mutant Type Structure Method: X-ray diffraction Resolution: 1.71  Å
PDB: 7TLK
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.85
TM score: 0.93473
Amino acid change:
G12S
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
M
M
T
T
E
E
Y
Y
K
K
L
L
V
V
V
V
V
V
10
|
G
G
A
A
G
S
G
G
V
V
G
G
K
K
S
S
A
A
L
L
20
|
T
T
I
I
Q
Q
L
L
I
I
Q
Q
N
N
H
H
F
F
V
V
30
|
D
D
E
E
Y
Y
D
D
P
P
T
T
I
I
E
E
D
D
S
S
40
|
Y
Y
R
R
K
K
Q
Q
V
V
V
V
I
I
D
D
G
G
E
E
50
|
T
T
C
C
L
L
L
L
D
D
I
I
L
L
D
D
T
T
A
A
60
|
G
G
Q
Q
E
E
E
E
Y
Y
S
S
A
A
M
M
R
R
D
D
70
|
Q
Q
Y
Y
M
M
R
R
T
T
G
G
E
E
G
G
F
F
L
L
80
|
C
C
V
V
F
F
A
A
I
I
N
N
N
N
T
T
K
K
S
S
90
|
F
F
E
E
D
D
I
I
H
H
H
H
Y
Y
R
R
E
E
Q
Q
100
|
I
I
K
K
R
R
V
V
K
K
D
D
S
S
E
E
D
D
V
V
110
|
P
P
M
M
V
V
L
L
V
V
G
G
N
N
K
K
C
C
D
D
120
|
L
L
P
P
S
S
R
R
T
T
V
V
D
D
T
T
K
K
Q
Q
130
|
A
A
Q
Q
D
D
L
L
A
A
R
R
S
S
Y
Y
G
G
I
I
140
|
P
P
F
F
I
I
E
E
T
T
S
S
A
A
K
K
T
T
R
R
150
|
Q
Q
G
G
V
V
D
D
D
D
A
A
F
F
Y
Y
T
T
L
L
160
|
V
V
R
R
E
E
I
I
R
R
K
K
H
H
K
K
E
E
K
K
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model Plasma Blood Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Next-generation sequencing assay; Circulating-free DNA assay
Experiment for
Drug Resistance		 Positron emission tomography/Computed tomography assay
Mechanism Description Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: Neurogenic locus notch homolog protein 1 (NOTCH1) [1]
Resistant Disease HER2 positive breast cancer [ICD-11: 2C60.8]
 Disease Info 
Molecule Alteration Missense mutation
p.V1676A
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Notch signaling pathway Regulation N.A.
In Vitro Model Plasma Blood Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Next-generation sequencing assay; Circulating-free DNA assay
Experiment for
Drug Resistance		 Positron emission tomography/Computed tomography assay
Mechanism Description Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: Neurogenic locus notch homolog protein 1 (NOTCH1) [1]
Resistant Disease HER2 positive breast cancer [ICD-11: 2C60.8]
 Disease Info 
Molecule Alteration Missense mutation
p.V1599M
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Notch signaling pathway Regulation N.A.
In Vitro Model Plasma Blood Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Next-generation sequencing assay; Circulating-free DNA assay
Experiment for
Drug Resistance		 Positron emission tomography/Computed tomography assay
Mechanism Description Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: Neurogenic locus notch homolog protein 1 (NOTCH1) [1]
Resistant Disease HER2 positive breast cancer [ICD-11: 2C60.8]
 Disease Info 
Molecule Alteration Missense mutation
p.S1689P
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Notch signaling pathway Regulation N.A.
In Vitro Model Plasma Blood Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Next-generation sequencing assay; Circulating-free DNA assay
Experiment for
Drug Resistance		 Positron emission tomography/Computed tomography assay
Mechanism Description Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: GTPase Nras (NRAS) [1]
Resistant Disease HER2 positive breast cancer [ICD-11: 2C60.8]
 Disease Info 
Molecule Alteration Missense mutation
p.V14A
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Plasma Blood Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Next-generation sequencing assay; Circulating-free DNA assay
Experiment for
Drug Resistance		 Positron emission tomography/Computed tomography assay
Mechanism Description Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: GTPase Nras (NRAS) [1]
Resistant Disease HER2 positive breast cancer [ICD-11: 2C60.8]
 Disease Info 
Molecule Alteration Missense mutation
p.F78L
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Plasma Blood Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Next-generation sequencing assay; Circulating-free DNA assay
Experiment for
Drug Resistance		 Positron emission tomography/Computed tomography assay
Mechanism Description Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: GTPase Nras (NRAS) [1]
Resistant Disease HER2 positive breast cancer [ICD-11: 2C60.8]
 Disease Info 
Molecule Alteration Missense mutation
p.F28S
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Plasma Blood Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Next-generation sequencing assay; Circulating-free DNA assay
Experiment for
Drug Resistance		 Positron emission tomography/Computed tomography assay
Mechanism Description Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: GTPase Nras (NRAS) [1]
Resistant Disease HER2 positive breast cancer [ICD-11: 2C60.8]
 Disease Info 
Molecule Alteration Missense mutation
p.A66T
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Plasma Blood Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Next-generation sequencing assay; Circulating-free DNA assay
Experiment for
Drug Resistance		 Positron emission tomography/Computed tomography assay
Mechanism Description Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: DNA mismatch repair protein Mlh1 (MLH1) [1]
Resistant Disease HER2 positive breast cancer [ICD-11: 2C60.8]
 Disease Info 
Molecule Alteration Missense mutation
p.V345A
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Plasma Blood Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Next-generation sequencing assay; Circulating-free DNA assay
Experiment for
Drug Resistance		 Positron emission tomography/Computed tomography assay
Mechanism Description Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: DNA mismatch repair protein Mlh1 (MLH1) [1]
Resistant Disease HER2 positive breast cancer [ICD-11: 2C60.8]
 Disease Info 
Molecule Alteration Missense mutation
p.R90Q
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Plasma Blood Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Next-generation sequencing assay; Circulating-free DNA assay
Experiment for
Drug Resistance		 Positron emission tomography/Computed tomography assay
Mechanism Description Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: DNA mismatch repair protein Mlh1 (MLH1) [1]
Resistant Disease HER2 positive breast cancer [ICD-11: 2C60.8]
 Disease Info 
Molecule Alteration Missense mutation
p.R74Q
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Plasma Blood Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Next-generation sequencing assay; Circulating-free DNA assay
Experiment for
Drug Resistance		 Positron emission tomography/Computed tomography assay
Mechanism Description Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: DNA mismatch repair protein Mlh1 (MLH1) [1]
Resistant Disease HER2 positive breast cancer [ICD-11: 2C60.8]
 Disease Info 
Molecule Alteration Missense mutation
p.A348V
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Plasma Blood Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Next-generation sequencing assay; Circulating-free DNA assay
Experiment for
Drug Resistance		 Positron emission tomography/Computed tomography assay
Mechanism Description Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: GTPase Hras (HRAS) [1]
Resistant Disease HER2 positive breast cancer [ICD-11: 2C60.8]
 Disease Info 
Molecule Alteration Missense mutation
p.V9A
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Plasma Blood Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Next-generation sequencing assay; Circulating-free DNA assay
Experiment for
Drug Resistance		 Positron emission tomography/Computed tomography assay
Mechanism Description Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: GTPase Hras (HRAS) [1]
Resistant Disease HER2 positive breast cancer [ICD-11: 2C60.8]
 Disease Info 
Molecule Alteration Missense mutation
p.T2A
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Plasma Blood Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Next-generation sequencing assay; Circulating-free DNA assay
Experiment for
Drug Resistance		 Positron emission tomography/Computed tomography assay
Mechanism Description Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: GTPase Hras (HRAS) [1]
Resistant Disease HER2 positive breast cancer [ICD-11: 2C60.8]
 Disease Info 
Molecule Alteration Missense mutation
p.S17N
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Plasma Blood Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Next-generation sequencing assay; Circulating-free DNA assay
Experiment for
Drug Resistance		 Positron emission tomography/Computed tomography assay
Mechanism Description Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: GTPase Hras (HRAS) [1]
Resistant Disease HER2 positive breast cancer [ICD-11: 2C60.8]
 Disease Info 
Molecule Alteration Missense mutation
p.Q61X
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Plasma Blood Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Next-generation sequencing assay; Circulating-free DNA assay
Experiment for
Drug Resistance		 Positron emission tomography/Computed tomography assay
Mechanism Description Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: GTPase Hras (HRAS) [1]
Resistant Disease HER2 positive breast cancer [ICD-11: 2C60.8]
 Disease Info 
Molecule Alteration Missense mutation
p.N26S
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Plasma Blood Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Next-generation sequencing assay; Circulating-free DNA assay
Experiment for
Drug Resistance		 Positron emission tomography/Computed tomography assay
Mechanism Description Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: GTPase Hras (HRAS) [1]
Resistant Disease HER2 positive breast cancer [ICD-11: 2C60.8]
 Disease Info 
Molecule Alteration Missense mutation
p.D54N
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Plasma Blood Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Next-generation sequencing assay; Circulating-free DNA assay
Experiment for
Drug Resistance		 Positron emission tomography/Computed tomography assay
Mechanism Description Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: Adenylate cyclase-stimulating G alpha protein (GNAS) [1]
Resistant Disease HER2 positive breast cancer [ICD-11: 2C60.8]
 Disease Info 
Molecule Alteration Missense mutation
p.R216L
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Plasma Blood Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Next-generation sequencing assay; Circulating-free DNA assay
Experiment for
Drug Resistance		 Positron emission tomography/Computed tomography assay
Mechanism Description Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: Adenylate cyclase-stimulating G alpha protein (GNAS) [1]
Resistant Disease HER2 positive breast cancer [ICD-11: 2C60.8]
 Disease Info 
Molecule Alteration Missense mutation
p.R216C
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Plasma Blood Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Next-generation sequencing assay; Circulating-free DNA assay
Experiment for
Drug Resistance		 Positron emission tomography/Computed tomography assay
Mechanism Description Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: Adenylate cyclase-stimulating G alpha protein (GNAS) [1]
Resistant Disease HER2 positive breast cancer [ICD-11: 2C60.8]
 Disease Info 
Molecule Alteration Missense mutation
p.R186H
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Plasma Blood Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Next-generation sequencing assay; Circulating-free DNA assay
Experiment for
Drug Resistance		 Positron emission tomography/Computed tomography assay
Mechanism Description Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: Adenylate cyclase-stimulating G alpha protein (GNAS) [1]
Resistant Disease HER2 positive breast cancer [ICD-11: 2C60.8]
 Disease Info 
Molecule Alteration Missense mutation
p.N203S
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Plasma Blood Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Next-generation sequencing assay; Circulating-free DNA assay
Experiment for
Drug Resistance		 Positron emission tomography/Computed tomography assay
Mechanism Description Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: Adenylate cyclase-stimulating G alpha protein (GNAS) [1]
Resistant Disease HER2 positive breast cancer [ICD-11: 2C60.8]
 Disease Info 
Molecule Alteration Missense mutation
p.M206V
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Plasma Blood Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Next-generation sequencing assay; Circulating-free DNA assay
Experiment for
Drug Resistance		 Positron emission tomography/Computed tomography assay
Mechanism Description Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: Adenylate cyclase-stimulating G alpha protein (GNAS) [1]
Resistant Disease HER2 positive breast cancer [ICD-11: 2C60.8]
 Disease Info 
Molecule Alteration Missense mutation
p.D214N
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Plasma Blood Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Next-generation sequencing assay; Circulating-free DNA assay
Experiment for
Drug Resistance		 Positron emission tomography/Computed tomography assay
Mechanism Description Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: Adenylate cyclase-stimulating G alpha protein (GNAS) [1]
Resistant Disease HER2 positive breast cancer [ICD-11: 2C60.8]
 Disease Info 
Molecule Alteration Missense mutation
p.D181G
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Plasma Blood Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Next-generation sequencing assay; Circulating-free DNA assay
Experiment for
Drug Resistance		 Positron emission tomography/Computed tomography assay
Mechanism Description Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: Epidermal growth factor receptor (EGFR) [1]
Resistant Disease HER2 positive breast cancer [ICD-11: 2C60.8]
 Disease Info 
Molecule Alteration Missense mutation
p.V292E
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Plasma Blood Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Next-generation sequencing assay; Circulating-free DNA assay
Experiment for
Drug Resistance		 Positron emission tomography/Computed tomography assay
Mechanism Description Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: Epidermal growth factor receptor (EGFR) [1]
Resistant Disease HER2 positive breast cancer [ICD-11: 2C60.8]
 Disease Info 
Molecule Alteration Missense mutation
p.R705G
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Plasma Blood Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Next-generation sequencing assay; Circulating-free DNA assay
Experiment for
Drug Resistance		 Positron emission tomography/Computed tomography assay
Mechanism Description Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: Epidermal growth factor receptor (EGFR) [1]
Resistant Disease HER2 positive breast cancer [ICD-11: 2C60.8]
 Disease Info 
Molecule Alteration Missense mutation
p.L760F
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Plasma Blood Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Next-generation sequencing assay; Circulating-free DNA assay
Experiment for
Drug Resistance		 Positron emission tomography/Computed tomography assay
Mechanism Description Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: Epidermal growth factor receptor (EGFR) [1]
Resistant Disease HER2 positive breast cancer [ICD-11: 2C60.8]
 Disease Info 
Molecule Alteration Missense mutation
p.K284E
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Plasma Blood Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Next-generation sequencing assay; Circulating-free DNA assay
Experiment for
Drug Resistance		 Positron emission tomography/Computed tomography assay
Mechanism Description Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: Epidermal growth factor receptor (EGFR) [1]
Resistant Disease HER2 positive breast cancer [ICD-11: 2C60.8]
 Disease Info 
Molecule Alteration Missense mutation
p.I706T
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Plasma Blood Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Next-generation sequencing assay; Circulating-free DNA assay
Experiment for
Drug Resistance		 Positron emission tomography/Computed tomography assay
Mechanism Description Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: Epidermal growth factor receptor (EGFR) [1]
Resistant Disease HER2 positive breast cancer [ICD-11: 2C60.8]
 Disease Info 
Molecule Alteration Missense mutation
p.G696E
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Plasma Blood Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Next-generation sequencing assay; Circulating-free DNA assay
Experiment for
Drug Resistance		 Positron emission tomography/Computed tomography assay
Mechanism Description Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: Epidermal growth factor receptor (EGFR) [1]
Resistant Disease HER2 positive breast cancer [ICD-11: 2C60.8]
 Disease Info 
Molecule Alteration Missense mutation
p.A822V
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Plasma Blood Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Next-generation sequencing assay; Circulating-free DNA assay
Experiment for
Drug Resistance		 Positron emission tomography/Computed tomography assay
Mechanism Description Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: Epidermal growth factor receptor (EGFR) [1]
Resistant Disease HER2 positive breast cancer [ICD-11: 2C60.8]
 Disease Info 
Molecule Alteration Missense mutation
p.V292M
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Plasma Blood Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Next-generation sequencing assay; Circulating-free DNA assay
Experiment for
Drug Resistance		 Positron emission tomography/Computed tomography assay
Mechanism Description Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: Epidermal growth factor receptor (EGFR) [1]
Resistant Disease HER2 positive breast cancer [ICD-11: 2C60.8]
 Disease Info 
Molecule Alteration Missense mutation
p.P741S
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Plasma Blood Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Next-generation sequencing assay; Circulating-free DNA assay
Experiment for
Drug Resistance		 Positron emission tomography/Computed tomography assay
Mechanism Description Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: Epidermal growth factor receptor (EGFR) [1]
Resistant Disease HER2 positive breast cancer [ICD-11: 2C60.8]
 Disease Info 
Molecule Alteration Missense mutation
p.G288D
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Plasma Blood Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Next-generation sequencing assay; Circulating-free DNA assay
Experiment for
Drug Resistance		 Positron emission tomography/Computed tomography assay
Mechanism Description Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: Epidermal growth factor receptor (EGFR) [1]
Resistant Disease HER2 positive breast cancer [ICD-11: 2C60.8]
 Disease Info 
Molecule Alteration Missense mutation
p.E711K
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Plasma Blood Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Next-generation sequencing assay; Circulating-free DNA assay
Experiment for
Drug Resistance		 Positron emission tomography/Computed tomography assay
Mechanism Description Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: Cadherin-1 (CDH1) [1]
Resistant Disease HER2 positive breast cancer [ICD-11: 2C60.8]
 Disease Info 
Molecule Alteration Missense mutation
p.A348V
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Plasma Blood Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Next-generation sequencing assay; Circulating-free DNA assay
Experiment for
Drug Resistance		 Positron emission tomography/Computed tomography assay
Mechanism Description Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: Cadherin-1 (CDH1) [1]
Resistant Disease HER2 positive breast cancer [ICD-11: 2C60.8]
 Disease Info 
Molecule Alteration Missense mutation
p.V345A
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Plasma Blood Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Next-generation sequencing assay; Circulating-free DNA assay
Experiment for
Drug Resistance		 Positron emission tomography/Computed tomography assay
Mechanism Description Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: Cadherin-1 (CDH1) [1]
Resistant Disease HER2 positive breast cancer [ICD-11: 2C60.8]
 Disease Info 
Molecule Alteration Missense mutation
p.R90Q
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Plasma Blood Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Next-generation sequencing assay; Circulating-free DNA assay
Experiment for
Drug Resistance		 Positron emission tomography/Computed tomography assay
Mechanism Description Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: Cadherin-1 (CDH1) [1]
Resistant Disease HER2 positive breast cancer [ICD-11: 2C60.8]
 Disease Info 
Molecule Alteration Missense mutation
p.R74Q
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Plasma Blood Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Next-generation sequencing assay; Circulating-free DNA assay
Experiment for
Drug Resistance		 Positron emission tomography/Computed tomography assay
Mechanism Description Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
References
Ref 1 Circulating-free DNA Mutation Associated with Response of Targeted Therapy in Human Epidermal Growth Factor Receptor 2-positive Metastatic Breast Cancer. Chin Med J (Engl). 2017 Mar 5;130(5):522-529. doi: 10.4103/0366-6999.200542.

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