m6A-centered Drug Response Information

General Information of the Drug (ID: M6ADRUG0058)
Name
PMID31239444-anti-PD1 antibody
Status Investigative [1]
Full List of m6A Targets Related to This Drug
C-X-C chemokine receptor type 4 (CXCR4)
 Target Info 
In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene [1]
Response Summary These findings demonstrate a crucial role of FTO as an m6A demethylase in promoting melanoma tumorigenesis and anti-PD-1 resistance, and suggest that the combination of FTO inhibition with anti-PD-1 blockade reduces the resistance to immunotherapy in melanoma. Knockdown of FTO increases m6A methylation in the critical protumorigenic melanoma cell-intrinsic genes including PD-1 (PDCD1), C-X-C chemokine receptor type 4 (CXCR4), and SOX10, leading to increased RNA decay through the m6A reader YTHDF2.
Responsed Disease Melanoma ICD-11: 2C30
 Disease Info 
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
 Regulator Info 
Target Regulation Up regulation
Pathway Response PD-L1 expression and PD-1 checkpoint pathway in cancer hsa05235
Cell Process mRNA decay
In-vitro Model B16-F10 Mouse melanoma Mus musculus CVCL_0159
CHL-1 Melanoma Homo sapiens CVCL_1122
624-mel Melanoma Homo sapiens CVCL_8054
NHEM (Normal Human Epidermal Melanocytes)
SK-MEL-30 Cutaneous melanoma Homo sapiens CVCL_0039
WM115 Melanoma Homo sapiens CVCL_0040
WM35 Melanoma Homo sapiens CVCL_0580
WM3670 Melanoma Homo sapiens CVCL_6799
WM793 Melanoma Homo sapiens CVCL_8787
In-vivo Model When the tumors reached a volume of 80-100 mm3, mice were treated with anti-PD-1 or isotype control antibody (200 ug/mouse) by i.p. injection, every other day for three times. For IFNγ blockade treatment, C57BL/6 mice were treated with anti-IFNγ antibody or isotype control IgG (250 ug/mouse) every other day after tumor cell inoculation.
Experiment 2 Reporting the m6A-centered Drug Response by This Target Gene [1]
Response Summary These findings demonstrate a crucial role of FTO as an m6A demethylase in promoting melanoma tumorigenesis and anti-PD-1 resistance, and suggest that the combination of FTO inhibition with anti-PD-1 blockade reduces the resistance to immunotherapy in melanoma. Knockdown of FTO increases m6A methylation in the critical protumorigenic melanoma cell-intrinsic genes including PD-1 (PDCD1), C-X-C chemokine receptor type 4 (CXCR4), and SOX10, leading to increased RNA decay through the m6A reader YTHDF2.
Responsed Disease Melanoma ICD-11: 2C30
 Disease Info 
Target Regulator YTH domain-containing family protein 2 (YTHDF2) READER
 Regulator Info 
Target Regulation Down regulation
Pathway Response PD-L1 expression and PD-1 checkpoint pathway in cancer hsa05235
Cell Process mRNA decay
In-vitro Model B16-F10 Mouse melanoma Mus musculus CVCL_0159
CHL-1 Melanoma Homo sapiens CVCL_1122
624-mel Melanoma Homo sapiens CVCL_8054
NHEM (Normal Human Epidermal Melanocytes)
SK-MEL-30 Cutaneous melanoma Homo sapiens CVCL_0039
WM115 Melanoma Homo sapiens CVCL_0040
WM35 Melanoma Homo sapiens CVCL_0580
WM3670 Melanoma Homo sapiens CVCL_6799
WM793 Melanoma Homo sapiens CVCL_8787
In-vivo Model When the tumors reached a volume of 80-100 mm3, mice were treated with anti-PD-1 or isotype control antibody (200 ug/mouse) by i.p. injection, every other day for three times. For IFNγ blockade treatment, C57BL/6 mice were treated with anti-IFNγ antibody or isotype control IgG (250 ug/mouse) every other day after tumor cell inoculation.
Programmed cell death 1 (PD-1)
 Target Info 
In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene [1]
Response Summary These findings demonstrate a crucial role of FTO as an m6A demethylase in promoting melanoma tumorigenesis and anti-PD-1 resistance, and suggest that the combination of FTO inhibition with anti-PD-1 blockade reduces the resistance to immunotherapy in melanoma. Knockdown of FTO increases m6A methylation in the critical protumorigenic melanoma cell-intrinsic genes including Programmed cell death 1 (PD-1) (PDCD1), CXCR4, and SOX10, leading to increased RNA decay through the m6A reader YTHDF2.
Responsed Disease Melanoma ICD-11: 2C30
 Disease Info 
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
 Regulator Info 
Target Regulation Up regulation
Pathway Response PD-L1 expression and PD-1 checkpoint pathway in cancer hsa05235
Cell Process mRNA decay
In-vitro Model B16-F10 Mouse melanoma Mus musculus CVCL_0159
CHL-1 Melanoma Homo sapiens CVCL_1122
624-mel Melanoma Homo sapiens CVCL_8054
NHEM (Normal Human Epidermal Melanocytes)
SK-MEL-30 Cutaneous melanoma Homo sapiens CVCL_0039
WM115 Melanoma Homo sapiens CVCL_0040
WM35 Melanoma Homo sapiens CVCL_0580
WM3670 Melanoma Homo sapiens CVCL_6799
WM793 Melanoma Homo sapiens CVCL_8787
In-vivo Model When the tumors reached a volume of 80-100 mm3, mice were treated with anti-PD-1 or isotype control antibody (200 ug/mouse) by i.p. injection, every other day for three times. For IFNγ blockade treatment, C57BL/6 mice were treated with anti-IFNγ antibody or isotype control IgG (250 ug/mouse) every other day after tumor cell inoculation.
Experiment 2 Reporting the m6A-centered Drug Response by This Target Gene [1]
Response Summary These findings demonstrate a crucial role of FTO as an m6A demethylase in promoting melanoma tumorigenesis and anti-PD-1 resistance, and suggest that the combination of FTO inhibition with anti-PD-1 blockade reduces the resistance to immunotherapy in melanoma. Knockdown of FTO increases m6A methylation in the critical protumorigenic melanoma cell-intrinsic genes including Programmed cell death 1 (PD-1) (PDCD1), CXCR4, and SOX10, leading to increased RNA decay through the m6A reader YTHDF2.
Responsed Disease Melanoma ICD-11: 2C30
 Disease Info 
Target Regulator YTH domain-containing family protein 2 (YTHDF2) READER
 Regulator Info 
Target Regulation Down regulation
Pathway Response PD-L1 expression and PD-1 checkpoint pathway in cancer hsa05235
Cell Process mRNA decay
In-vitro Model B16-F10 Mouse melanoma Mus musculus CVCL_0159
CHL-1 Melanoma Homo sapiens CVCL_1122
624-mel Melanoma Homo sapiens CVCL_8054
NHEM (Normal Human Epidermal Melanocytes)
SK-MEL-30 Cutaneous melanoma Homo sapiens CVCL_0039
WM115 Melanoma Homo sapiens CVCL_0040
WM35 Melanoma Homo sapiens CVCL_0580
WM3670 Melanoma Homo sapiens CVCL_6799
WM793 Melanoma Homo sapiens CVCL_8787
In-vivo Model When the tumors reached a volume of 80-100 mm3, mice were treated with anti-PD-1 or isotype control antibody (200 ug/mouse) by i.p. injection, every other day for three times. For IFNγ blockade treatment, C57BL/6 mice were treated with anti-IFNγ antibody or isotype control IgG (250 ug/mouse) every other day after tumor cell inoculation.
Transcription factor SOX-10 (SOX10)
 Target Info 
In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene [1]
Response Summary These findings demonstrate a crucial role of FTO as an m6A demethylase in promoting melanoma tumorigenesis and anti-PD-1 resistance, and suggest that the combination of FTO inhibition with anti-PD-1 blockade reduces the resistance to immunotherapy in melanoma. Knockdown of FTO increases m6A methylation in the critical protumorigenic melanoma cell-intrinsic genes including PD-1 (PDCD1), CXCR4, and Transcription factor SOX-10 (SOX10), leading to increased RNA decay through the m6A reader YTHDF2.
Responsed Disease Melanoma ICD-11: 2C30
 Disease Info 
Target Regulator YTH domain-containing family protein 2 (YTHDF2) READER
 Regulator Info 
Target Regulation Down regulation
Pathway Response PD-L1 expression and PD-1 checkpoint pathway in cancer hsa05235
Cell Process mRNA decay
In-vitro Model B16-F10 Mouse melanoma Mus musculus CVCL_0159
CHL-1 Melanoma Homo sapiens CVCL_1122
624-mel Melanoma Homo sapiens CVCL_8054
NHEM (Normal Human Epidermal Melanocytes)
SK-MEL-30 Cutaneous melanoma Homo sapiens CVCL_0039
WM115 Melanoma Homo sapiens CVCL_0040
WM35 Melanoma Homo sapiens CVCL_0580
WM3670 Melanoma Homo sapiens CVCL_6799
WM793 Melanoma Homo sapiens CVCL_8787
In-vivo Model When the tumors reached a volume of 80-100 mm3, mice were treated with anti-PD-1 or isotype control antibody (200 ug/mouse) by i.p. injection, every other day for three times. For IFNγ blockade treatment, C57BL/6 mice were treated with anti-IFNγ antibody or isotype control IgG (250 ug/mouse) every other day after tumor cell inoculation.
Experiment 2 Reporting the m6A-centered Drug Response by This Target Gene [1]
Response Summary These findings demonstrate a crucial role of FTO as an m6A demethylase in promoting melanoma tumorigenesis and anti-PD-1 resistance, and suggest that the combination of FTO inhibition with anti-PD-1 blockade reduces the resistance to immunotherapy in melanoma. Knockdown of FTO increases m6A methylation in the critical protumorigenic melanoma cell-intrinsic genes including PD-1 (PDCD1), CXCR4, and Transcription factor SOX-10 (SOX10), leading to increased RNA decay through the m6A reader YTHDF2.
Responsed Disease Melanoma ICD-11: 2C30
 Disease Info 
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
 Regulator Info 
Target Regulation Up regulation
Pathway Response PD-L1 expression and PD-1 checkpoint pathway in cancer hsa05235
Cell Process mRNA decay
In-vitro Model B16-F10 Mouse melanoma Mus musculus CVCL_0159
CHL-1 Melanoma Homo sapiens CVCL_1122
624-mel Melanoma Homo sapiens CVCL_8054
NHEM (Normal Human Epidermal Melanocytes)
SK-MEL-30 Cutaneous melanoma Homo sapiens CVCL_0039
WM115 Melanoma Homo sapiens CVCL_0040
WM35 Melanoma Homo sapiens CVCL_0580
WM3670 Melanoma Homo sapiens CVCL_6799
WM793 Melanoma Homo sapiens CVCL_8787
In-vivo Model When the tumors reached a volume of 80-100 mm3, mice were treated with anti-PD-1 or isotype control antibody (200 ug/mouse) by i.p. injection, every other day for three times. For IFNγ blockade treatment, C57BL/6 mice were treated with anti-IFNγ antibody or isotype control IgG (250 ug/mouse) every other day after tumor cell inoculation.
References
Ref 1 m(6)A mRNA demethylase FTO regulates melanoma tumorigenicity and response to anti-PD-1 blockade. Nat Commun. 2019 Jun 25;10(1):2782. doi: 10.1038/s41467-019-10669-0.