Disease Information

General Information of the Disease (ID: DIS00079)
Name
Pleural mesothelioma
ICD
ICD-11: 2C26
Resistance Map
Type(s) of Resistant Mechanism of This Disease
  ADTT: Aberration of the Drug's Therapeutic Target
  EADR: Epigenetic Alteration of DNA, RNA or Protein
  IDUE: Irregularity in Drug Uptake and Drug Efflux
  UAPP: Unusual Activation of Pro-survival Pathway
Drug Resistance Data Categorized by Drug
Approved Drug(s)
6 drug(s) in total
Click to Show/Hide the Full List of Drugs
Cisplatin
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: Pvt1 oncogene (PVT1) [1]
Resistant Disease Malignant pleural mesothelioma [ICD-11: 2C26.0]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Drug Cisplatin
 Drug Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell proliferation Activation hsa05200
In Vitro Model MSTO-211H cells Lung Homo sapiens (Human) CVCL_1430
NCI-H2052 cells Lung Homo sapiens (Human) CVCL_1518
NCI-H2452 cells Lung Homo sapiens (Human) CVCL_1553
NCI-H28 cells Lung Homo sapiens (Human) CVCL_1555
HCT-4012 cells Lung Homo sapiens (Human) CVCL_IT30
HP10 cells Lung Homo sapiens (Human) N.A.
HP3 cells Lung Homo sapiens (Human) CVCL_C311
HP5 cells Lung Homo sapiens (Human) N.A.
HP7 cells Lung Homo sapiens (Human) N.A.
HP9 cells Lung Homo sapiens (Human) N.A.
MET-5A cells Lung Homo sapiens (Human) CVCL_3749
Meso cells Lung Homo sapiens (Human) CVCL_5759
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 MTS assay
Mechanism Description c-Myc and PVT1 co-amplification is frequent in MPM. C-MYC and PVT1 cooperation helps to stimulate proliferation, decrease sensitivity to platinum therapy, and reduce apoptosis. Both genes also help to regulate apoptosis-related genes, with C-MYC revealing a tendency to maintain a balance between pro-apoptotic and anti-apoptotic genes, whereas PVT1 revealed a tendency to upregulate pro-apoptotic genes and downregulate anti-apoptotic genes, thereby helping to suppress apoptosis.
Key Molecule: hsa-mir-15a [2]
Resistant Disease Malignant pleural mesothelioma [ICD-11: 2C26.0]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Drug Cisplatin
 Drug Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model MSTO-211H cells Lung Homo sapiens (Human) CVCL_1430
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 SYBR Green-based assay
Mechanism Description Expression of miR-15a, miR-16 and miR-34a was downregulated in MPM cells with acquired drug resistance. Transfection with miR-15a or miR-16 mimics reversed the resistance to cisplatin, gemcitabine or vinorelbine, whereas miR-34a reversed cisplatin and vinorelbine resistance only.
Key Molecule: hsa-mir-15a [2]
Resistant Disease Malignant pleural mesothelioma [ICD-11: 2C26.0]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Drug Cisplatin
 Drug Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model MSTO-211H cells Lung Homo sapiens (Human) CVCL_1430
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 SYBR Green-based assay
Mechanism Description Expression of miR-15a, miR-16 and miR-34a was downregulated in MPM cells with acquired drug resistance. Transfection with miR-15a or miR-16 mimics reversed the resistance to cisplatin, gemcitabine or vinorelbine, whereas miR-34a reversed cisplatin and vinorelbine resistance only.
Key Molecule: hsa-mir-16 [2]
Resistant Disease Malignant pleural mesothelioma [ICD-11: 2C26.0]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Drug Cisplatin
 Drug Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model MSTO-211H cells Lung Homo sapiens (Human) CVCL_1430
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 SYBR Green-based assay
Mechanism Description Expression of miR-15a, miR-16 and miR-34a was downregulated in MPM cells with acquired drug resistance. Transfection with miR-15a or miR-16 mimics reversed the resistance to cisplatin, gemcitabine or vinorelbine, whereas miR-34a reversed cisplatin and vinorelbine resistance only.
Key Molecule: hsa-mir-16 [2]
Resistant Disease Malignant pleural mesothelioma [ICD-11: 2C26.0]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Drug Cisplatin
 Drug Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model MSTO-211H cells Lung Homo sapiens (Human) CVCL_1430
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 SYBR Green-based assay
Mechanism Description Expression of miR-15a, miR-16 and miR-34a was downregulated in MPM cells with acquired drug resistance. Transfection with miR-15a or miR-16 mimics reversed the resistance to cisplatin, gemcitabine or vinorelbine, whereas miR-34a reversed cisplatin and vinorelbine resistance only.
Key Molecule: Forkhead box protein O3 (FOXO3) [2]
Resistant Disease Malignant pleural mesothelioma [ICD-11: 2C26.0]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Drug Cisplatin
 Drug Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model MSTO-211H cells Lung Homo sapiens (Human) CVCL_1430
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 SYBR Green-based assay
Mechanism Description Expression of miR-15a, miR-16 and miR-34a was downregulated in MPM cells with acquired drug resistance. Transfection with miR-15a or miR-16 mimics reversed the resistance to cisplatin, gemcitabine or vinorelbine, whereas miR-34a reversed cisplatin and vinorelbine resistance only.
Key Molecule: Forkhead box protein O3 (FOXO3) [2]
Resistant Disease Malignant pleural mesothelioma [ICD-11: 2C26.0]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Drug Cisplatin
 Drug Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model MSTO-211H cells Lung Homo sapiens (Human) CVCL_1430
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 SYBR Green-based assay
Mechanism Description Expression of miR-15a, miR-16 and miR-34a was downregulated in MPM cells with acquired drug resistance. Transfection with miR-15a or miR-16 mimics reversed the resistance to cisplatin, gemcitabine or vinorelbine, whereas miR-34a reversed cisplatin and vinorelbine resistance only.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Myc proto-oncogene protein (MYC) [1]
Resistant Disease Malignant pleural mesothelioma [ICD-11: 2C26.0]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Drug Cisplatin
 Drug Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell proliferation Activation hsa05200
In Vitro Model MSTO-211H cells Lung Homo sapiens (Human) CVCL_1430
NCI-H2052 cells Lung Homo sapiens (Human) CVCL_1518
NCI-H2452 cells Lung Homo sapiens (Human) CVCL_1553
NCI-H28 cells Lung Homo sapiens (Human) CVCL_1555
HCT-4012 cells Lung Homo sapiens (Human) CVCL_IT30
HP10 cells Lung Homo sapiens (Human) N.A.
HP3 cells Lung Homo sapiens (Human) CVCL_C311
HP5 cells Lung Homo sapiens (Human) N.A.
HP7 cells Lung Homo sapiens (Human) N.A.
HP9 cells Lung Homo sapiens (Human) N.A.
MET-5A cells Lung Homo sapiens (Human) CVCL_3749
Meso cells Lung Homo sapiens (Human) CVCL_5759
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 MTS assay
Mechanism Description c-Myc and PVT1 co-amplification is frequent in MPM. C-MYC and PVT1 cooperation helps to stimulate proliferation, decrease sensitivity to platinum therapy, and reduce apoptosis. Both genes also help to regulate apoptosis-related genes, with C-MYC revealing a tendency to maintain a balance between pro-apoptotic and anti-apoptotic genes, whereas PVT1 revealed a tendency to upregulate pro-apoptotic genes and downregulate anti-apoptotic genes, thereby helping to suppress apoptosis.
Gemcitabine
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: hsa-mir-16 [3]
Sensitive Disease Malignant pleural mesothelioma [ICD-11: 2C26.0]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Drug Gemcitabine
 Drug Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model MET-5A cells Lung Homo sapiens (Human) CVCL_3749
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 RT-qPCR
Experiment for
Drug Resistance		 MTT assay; Colony formation assay
Mechanism Description Growth inhibition caused by miR-16 correlated with downregulation of target genes including Bcl-2 and CCND1, and miR-16 re-expression sensitised MPM cells to pemetrexed and gemcitabine.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Apoptosis regulator Bcl-2 (BCL2) [3]
Sensitive Disease Malignant pleural mesothelioma [ICD-11: 2C26.0]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Drug Gemcitabine
 Drug Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model MET-5A cells Lung Homo sapiens (Human) CVCL_3749
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTT assay; Colony formation assay
Mechanism Description Growth inhibition caused by miR-16 correlated with downregulation of target genes including Bcl-2 and CCND1, and miR-16 re-expression sensitised MPM cells to pemetrexed and gemcitabine.
Key Molecule: G1/S-specific cyclin-D1 (CCND1) [3]
Sensitive Disease Malignant pleural mesothelioma [ICD-11: 2C26.0]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Drug Gemcitabine
 Drug Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model MET-5A cells Lung Homo sapiens (Human) CVCL_3749
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTT assay; Colony formation assay
Mechanism Description Growth inhibition caused by miR-16 correlated with downregulation of target genes including Bcl-2 and CCND1, and miR-16 re-expression sensitised MPM cells to pemetrexed and gemcitabine.
Paclitaxel
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: hsa-mir-149 [4]
Resistant Disease Malignant pleural mesothelioma [ICD-11: 2C26.0]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Drug Paclitaxel
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model A549 cells Lung Homo sapiens (Human) CVCL_0023
H69 cells Lung Homo sapiens (Human) CVCL_8121
H69AR cells Lung Homo sapiens (Human) CVCL_3513
MSTO-211H cells Lung Homo sapiens (Human) CVCL_1430
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 MTT assay
Mechanism Description micro-RNA149 confers taxane resistance to malignant mesothelioma cells via upregulation of P-glycoprotein expression.
       Irregularity in Drug Uptake and Drug Efflux (IDUE) Click to Show/Hide
Key Molecule: ATP-binding cassette sub-family B5 (ABCB5) [4]
Resistant Disease Malignant pleural mesothelioma [ICD-11: 2C26.0]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Drug Paclitaxel
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model A549 cells Lung Homo sapiens (Human) CVCL_0023
H69 cells Lung Homo sapiens (Human) CVCL_8121
H69AR cells Lung Homo sapiens (Human) CVCL_3513
MSTO-211H cells Lung Homo sapiens (Human) CVCL_1430
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTT assay
Mechanism Description micro-RNA149 confers taxane resistance to malignant mesothelioma cells via upregulation of P-glycoprotein expression.
Pemetrexed
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: Thymidylate synthase (TYMS) [5]
Resistant Disease Malignant pleural mesothelioma [ICD-11: 2C26.0]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Drug Pemetrexed
 Drug Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model MSTO-211H cells Lung Homo sapiens (Human) CVCL_1430
Plat-A cells Hepato Homo sapiens (Human) CVCL_B489
TCC-MESO-2 cells Bone and hypodermis Homo sapiens (Human) CVCL_E264
Experiment for
Molecule Alteration		 Western blotting assay
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description TYMS overexpression significantly increased drug resistance in the parental cells.The results of chromatin immunoprecipitation-quantitative polymerase chain reaction (ChIP-qPCR) assays suggested that H3K27 acetylation in the 5'-UTR of TYMS may promote its expression in drug-resistant cells.
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: hsa-mir-379 [6]
Sensitive Disease Malignant pleural mesothelioma [ICD-11: 2C26.0]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Drug Pemetrexed
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell invasion Inhibition hsa05200
Cell proliferation Inhibition hsa05200
In Vitro Model MSTO-211H cells Lung Homo sapiens (Human) CVCL_1430
ACC-MESO1 cells Lung Homo sapiens (Human) CVCL_5113
ACC-MESO4 cells Lung Homo sapiens (Human) CVCL_5114
NCI-H2052 cells Lung Homo sapiens (Human) CVCL_1518
NCI-H2452 cells Lung Homo sapiens (Human) CVCL_1553
NCI-H28 cells Lung Homo sapiens (Human) CVCL_1555
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 MTS assay
Mechanism Description miR-379 and miR-411 play a key role in the carcinogenesis of MPM cells by targeting IL-18 and contributing to the sensitivity of MPM cells to SAHA and PEM.
Key Molecule: hsa-mir-411 [6]
Sensitive Disease Malignant pleural mesothelioma [ICD-11: 2C26.0]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Drug Pemetrexed
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell invasion Inhibition hsa05200
Cell proliferation Inhibition hsa05200
In Vitro Model MSTO-211H cells Lung Homo sapiens (Human) CVCL_1430
ACC-MESO1 cells Lung Homo sapiens (Human) CVCL_5113
ACC-MESO4 cells Lung Homo sapiens (Human) CVCL_5114
NCI-H2052 cells Lung Homo sapiens (Human) CVCL_1518
NCI-H2452 cells Lung Homo sapiens (Human) CVCL_1553
NCI-H28 cells Lung Homo sapiens (Human) CVCL_1555
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 MTS assay
Mechanism Description miR-379 and miR-411 play a key role in the carcinogenesis of MPM cells by targeting IL-18 and contributing to the sensitivity of MPM cells to SAHA and PEM.
Key Molecule: hsa-mir-16 [3]
Sensitive Disease Malignant pleural mesothelioma [ICD-11: 2C26.0]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Drug Pemetrexed
 Drug Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model MET-5A cells Lung Homo sapiens (Human) CVCL_3749
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 RT-qPCR
Experiment for
Drug Resistance		 MTT assay; Colony formation assay
Mechanism Description Growth inhibition caused by miR-16 correlated with downregulation of target genes including Bcl-2 and CCND1, and miR-16 re-expression sensitised MPM cells to pemetrexed and gemcitabine.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Interleukin-18 (IL18) [6]
Sensitive Disease Malignant pleural mesothelioma [ICD-11: 2C26.0]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Drug Pemetrexed
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell invasion Inhibition hsa05200
Cell proliferation Inhibition hsa05200
In Vitro Model MSTO-211H cells Lung Homo sapiens (Human) CVCL_1430
ACC-MESO1 cells Lung Homo sapiens (Human) CVCL_5113
ACC-MESO4 cells Lung Homo sapiens (Human) CVCL_5114
NCI-H2052 cells Lung Homo sapiens (Human) CVCL_1518
NCI-H2452 cells Lung Homo sapiens (Human) CVCL_1553
NCI-H28 cells Lung Homo sapiens (Human) CVCL_1555
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 MTS assay
Mechanism Description miR-379 and miR-411 play a key role in the carcinogenesis of MPM cells by targeting IL-18 and contributing to the sensitivity of MPM cells to SAHA and PEM.
Key Molecule: Apoptosis regulator Bcl-2 (BCL2) [3]
Sensitive Disease Malignant pleural mesothelioma [ICD-11: 2C26.0]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Drug Pemetrexed
 Drug Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model MET-5A cells Lung Homo sapiens (Human) CVCL_3749
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTT assay; Colony formation assay
Mechanism Description Growth inhibition caused by miR-16 correlated with downregulation of target genes including Bcl-2 and CCND1, and miR-16 re-expression sensitised MPM cells to pemetrexed and gemcitabine.
Key Molecule: G1/S-specific cyclin-D1 (CCND1) [3]
Sensitive Disease Malignant pleural mesothelioma [ICD-11: 2C26.0]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Drug Pemetrexed
 Drug Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model MET-5A cells Lung Homo sapiens (Human) CVCL_3749
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTT assay; Colony formation assay
Mechanism Description Growth inhibition caused by miR-16 correlated with downregulation of target genes including Bcl-2 and CCND1, and miR-16 re-expression sensitised MPM cells to pemetrexed and gemcitabine.
Vinorelbine
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: hsa-mir-15a [2]
Resistant Disease Malignant pleural mesothelioma [ICD-11: 2C26.0]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Drug Vinorelbine
 Drug Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model MSTO-211H cells Lung Homo sapiens (Human) CVCL_1430
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 SYBR Green-based assay
Mechanism Description Expression of miR-15a, miR-16 and miR-34a was downregulated in MPM cells with acquired drug resistance. Transfection with miR-15a or miR-16 mimics reversed the resistance to cisplatin, gemcitabine or vinorelbine, whereas miR-34a reversed cisplatin and vinorelbine resistance only.
Key Molecule: hsa-mir-15a [2]
Resistant Disease Malignant pleural mesothelioma [ICD-11: 2C26.0]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Drug Vinorelbine
 Drug Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model MSTO-211H cells Lung Homo sapiens (Human) CVCL_1430
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 SYBR Green-based assay
Mechanism Description Expression of miR-15a, miR-16 and miR-34a was downregulated in MPM cells with acquired drug resistance. Transfection with miR-15a or miR-16 mimics reversed the resistance to cisplatin, gemcitabine or vinorelbine, whereas miR-34a reversed cisplatin and vinorelbine resistance only.
Key Molecule: hsa-mir-16 [2]
Resistant Disease Malignant pleural mesothelioma [ICD-11: 2C26.0]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Drug Vinorelbine
 Drug Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model MSTO-211H cells Lung Homo sapiens (Human) CVCL_1430
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 SYBR Green-based assay
Mechanism Description Expression of miR-15a, miR-16 and miR-34a was downregulated in MPM cells with acquired drug resistance. Transfection with miR-15a or miR-16 mimics reversed the resistance to cisplatin, gemcitabine or vinorelbine, whereas miR-34a reversed cisplatin and vinorelbine resistance only.
Key Molecule: hsa-mir-16 [2]
Resistant Disease Malignant pleural mesothelioma [ICD-11: 2C26.0]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Drug Vinorelbine
 Drug Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model MSTO-211H cells Lung Homo sapiens (Human) CVCL_1430
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 SYBR Green-based assay
Mechanism Description Expression of miR-15a, miR-16 and miR-34a was downregulated in MPM cells with acquired drug resistance. Transfection with miR-15a or miR-16 mimics reversed the resistance to cisplatin, gemcitabine or vinorelbine, whereas miR-34a reversed cisplatin and vinorelbine resistance only.
Key Molecule: Forkhead box protein O3 (FOXO3) [2]
Resistant Disease Malignant pleural mesothelioma [ICD-11: 2C26.0]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Drug Vinorelbine
 Drug Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model MSTO-211H cells Lung Homo sapiens (Human) CVCL_1430
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 SYBR Green-based assay
Mechanism Description Expression of miR-15a, miR-16 and miR-34a was downregulated in MPM cells with acquired drug resistance. Transfection with miR-15a or miR-16 mimics reversed the resistance to cisplatin, gemcitabine or vinorelbine, whereas miR-34a reversed cisplatin and vinorelbine resistance only.
Key Molecule: Forkhead box protein O3 (FOXO3) [2]
Resistant Disease Malignant pleural mesothelioma [ICD-11: 2C26.0]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Drug Vinorelbine
 Drug Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model MSTO-211H cells Lung Homo sapiens (Human) CVCL_1430
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 SYBR Green-based assay
Mechanism Description Expression of miR-15a, miR-16 and miR-34a was downregulated in MPM cells with acquired drug resistance. Transfection with miR-15a or miR-16 mimics reversed the resistance to cisplatin, gemcitabine or vinorelbine, whereas miR-34a reversed cisplatin and vinorelbine resistance only.
Vorinostat
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: hsa-mir-379 [6]
Sensitive Disease Malignant pleural mesothelioma [ICD-11: 2C26.0]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Drug Vorinostat
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell invasion Inhibition hsa05200
Cell proliferation Inhibition hsa05200
In Vitro Model MSTO-211H cells Lung Homo sapiens (Human) CVCL_1430
ACC-MESO1 cells Lung Homo sapiens (Human) CVCL_5113
ACC-MESO4 cells Lung Homo sapiens (Human) CVCL_5114
NCI-H2052 cells Lung Homo sapiens (Human) CVCL_1518
NCI-H2452 cells Lung Homo sapiens (Human) CVCL_1553
NCI-H28 cells Lung Homo sapiens (Human) CVCL_1555
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 MTS assay
Mechanism Description miR-379 and miR-411 play a key role in the carcinogenesis of MPM cells by targeting IL-18 and contributing to the sensitivity of MPM cells to SAHA and PEM.
Key Molecule: hsa-mir-411 [6]
Sensitive Disease Malignant pleural mesothelioma [ICD-11: 2C26.0]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Drug Vorinostat
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell invasion Inhibition hsa05200
Cell proliferation Inhibition hsa05200
In Vitro Model MSTO-211H cells Lung Homo sapiens (Human) CVCL_1430
ACC-MESO1 cells Lung Homo sapiens (Human) CVCL_5113
ACC-MESO4 cells Lung Homo sapiens (Human) CVCL_5114
NCI-H2052 cells Lung Homo sapiens (Human) CVCL_1518
NCI-H2452 cells Lung Homo sapiens (Human) CVCL_1553
NCI-H28 cells Lung Homo sapiens (Human) CVCL_1555
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 MTS assay
Mechanism Description miR-379 and miR-411 play a key role in the carcinogenesis of MPM cells by targeting IL-18 and contributing to the sensitivity of MPM cells to SAHA and PEM.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Interleukin-18 (IL18) [6]
Sensitive Disease Malignant pleural mesothelioma [ICD-11: 2C26.0]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Drug Vorinostat
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell invasion Inhibition hsa05200
Cell proliferation Inhibition hsa05200
In Vitro Model MSTO-211H cells Lung Homo sapiens (Human) CVCL_1430
ACC-MESO1 cells Lung Homo sapiens (Human) CVCL_5113
ACC-MESO4 cells Lung Homo sapiens (Human) CVCL_5114
NCI-H2052 cells Lung Homo sapiens (Human) CVCL_1518
NCI-H2452 cells Lung Homo sapiens (Human) CVCL_1553
NCI-H28 cells Lung Homo sapiens (Human) CVCL_1555
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 MTS assay
Mechanism Description miR-379 and miR-411 play a key role in the carcinogenesis of MPM cells by targeting IL-18 and contributing to the sensitivity of MPM cells to SAHA and PEM.
Clinical Trial Drug(s)
1 drug(s) in total
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Apitolisib
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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: PI3-kinase alpha (PIK3CA) [7]
Sensitive Disease Malignant pleural mesothelioma [ICD-11: 2C26.0]
Molecule Alteration Missense mutation
p.R88Q (c.263G>A)
 Molecule Info 
Sensitive Drug Apitolisib
 Drug Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model . .
Experiment for
Molecule Alteration		 DxS allele-specific PCR; qRT-PCR assays; Sanger sequencing assay
Experiment for
Drug Resistance		 CTCAE assay
References
Ref 1 Frequent coamplification and cooperation between C-MYC and PVT1 oncogenes promote malignant pleural mesothelioma. J Thorac Oncol. 2014 Jul;9(7):998-1007. doi: 10.1097/JTO.0000000000000202.
Ref 2 Tumour suppressor microRNAs contribute to drug resistance in malignant pleural mesothelioma by targeting anti-apoptotic pathways .Cancer Drug Resist. 2019 Dec 19;2(4):1193-1206. doi: 10.20517/cdr.2019.41. eCollection 2019. 10.20517/cdr.2019.41
Ref 3 Restoring expression of miR-16: a novel approach to therapy for malignant pleural mesothelioma. Ann Oncol. 2013 Dec;24(12):3128-35. doi: 10.1093/annonc/mdt412. Epub 2013 Oct 22.
Ref 4 Micro-RNA149 confers taxane resistance to malignant mesothelioma cells via regulation of P-glycoprotein expression. Cancer Biol Ther. 2018 Mar 4;19(3):181-187. doi: 10.1080/15384047.2017.1415677. Epub 2018 Jan 15.
Ref 5 Upregulation of Thymidylate Synthase Induces Pemetrexed Resistance in Malignant Pleural Mesothelioma .Front Pharmacol. 2021 Sep 27;12:718675. doi: 10.3389/fphar.2021.718675. eCollection 2021. 10.3389/fphar.2021.718675
Ref 6 MiR-379/411 cluster regulates IL-18 and contributes to drug resistance in malignant pleural mesothelioma. Oncol Rep. 2014 Dec;32(6):2365-72. doi: 10.3892/or.2014.3481. Epub 2014 Sep 16.
Ref 7 Phase I Study of Apitolisib (GDC-0980), Dual Phosphatidylinositol-3-Kinase and Mammalian Target of Rapamycin Kinase Inhibitor, in Patients with Advanced Solid TumorsClin Cancer Res. 2016 Jun 15;22(12):2874-84. doi: 10.1158/1078-0432.CCR-15-2225. Epub 2016 Jan 19.
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