| Target General Information |
| Target ID |
T89055
|
| Target Name |
Dual specificity mitogen-activated protein kinase kinase 2 (MAP2K2) |
| Gene Name |
MAP2K2 |
| Species |
Homo sapiens |
| UniProt ID |
MP2K2_HUMAN |
| Sequence |
MLARRKPVLPALTINPTIAEGPSPTSEGASEANLVDLQKKLEELELDEQQKKRLEAFLTQ
KAKVGELKDDDFERISELGAGNGGVVTKVQHRPSGLIMARKLIHLEIKPAIRNQIIRELQ
VLHECNSPYIVGFYGAFYSDGEISICMEHMDGGSLDQVLKEAKRIPEEILGKVSIAVLRG
LAYLREKHQIMHRDVKPSNILVNSRGEIKLCDFGVSGQLIDSMANSFVGTRSYMAPERLQ
GTHYSVQSDIWSMGLSLVELAVGRYPIPPPDAKELEAIFGRPVVDGEEGEPHSISPRPRP
PGRPVSGHGMDSRPAMAIFELLDYIVNEPPPKLPNGVFTPDFQEFVNKCLIKNPAERADL
KMLTNHTFIKRSEVEEVDFAGWLCKTLRLNQPGTPTRTAV [Homo sapiens]
|
| Drug and Corresponding Resistance Mutations |
| Mutation Info |
Missense: C125S |
| Drugs |
| Drug Name |
Vemurafenib |
Drug Info
|
[1] |
| Targeted Disease |
Melanoma |
| Mutation Prevalence |
1 out of 76 patients |
|
| Drug Name |
Trametinib |
Drug Info
|
[1] |
| Targeted Disease |
Cutaneous Melanoma |
| Mutation Prevalence |
1 out of 4 patients |
|
| Drug Name |
Dabrafenib |
Drug Info
|
[1], [6] |
| Targeted Disease |
Melanoma |
| Mutation Prevalence |
2 out of 10 patients |
|
| Mutation Info |
Missense: E207K |
| Drugs |
| Drug Name |
Dabrafenib |
Drug Info
|
[6] |
| Targeted Disease |
Melanoma |
| Mutation Prevalence |
1 out of 10 patients |
|
| Mutation Info |
Missense: F57C |
| Drugs |
| Drug Name |
Vemurafenib |
Drug Info
|
[3] |
| Targeted Disease |
Melanoma |
| Mutation Prevalence |
1 out of 30 patients |
|
| Mutation Info |
Missense: L46F |
| Drugs |
| Drug Name |
Trametinib |
Drug Info
|
[1] |
| Targeted Disease |
Cutaneous Melanoma |
|
| Drug Name |
Dabrafenib |
Drug Info
|
[1] |
| Targeted Disease |
Melanoma |
| Mutation Prevalence |
3 out of 76 patients |
|
| Mutation Info |
Missense: N126D |
| Drugs |
| Drug Name |
Trametinib |
Drug Info
|
[1] |
| Targeted Disease |
Cutaneous Melanoma |
|
| Drug Name |
Dabrafenib |
Drug Info
|
[1] |
| Targeted Disease |
Melanoma |
| Mutation Prevalence |
1 out of 76 patients |
|
| Mutation Info |
Missense: Q60P |
| Drugs |
| Drug Name |
Vemurafenib |
Drug Info
|
[2] |
| Targeted Disease |
Melanoma |
| Mutation Prevalence |
3 out of 5 patients |
|
| Drug Name |
Dabrafenib |
Drug Info
|
[2], [5] |
| Targeted Disease |
Melanoma |
| Mutation Prevalence |
3 out of 5 patients |
|
| Drug Name |
Tremetinib |
Drug Info
|
[2] |
| Targeted Disease |
Cutaneous Melanoma |
| Mutation Prevalence |
3 out of 5 patients |
|
| Mutation Info |
Missense: V215E |
| Drugs |
| Drug Name |
PD0325901 |
Drug Info
|
[4] |
| Targeted Disease |
Cancer; Non-small Cell Lung Cancer |
|
| Mutation Info |
Missense: V35M |
| Drugs |
| Drug Name |
Vemurafenib |
Drug Info
|
[1] |
| Targeted Disease |
Melanoma |
| Mutation Prevalence |
1 out of 76 patients |
|
| Drug Name |
Trametinib |
Drug Info
|
[1] |
| Targeted Disease |
Cutaneous Melanoma |
|
| Drug Name |
Dabrafenib |
Drug Info
|
[1] |
| Targeted Disease |
Melanoma |
|
| References |
| REF 1 |
The genetic landscape of clinical resistance to RAF inhibition in metastatic melanoma. Cancer Discov. 2014 Jan;4(1):94-109.
|
| REF 2 |
MAP kinase pathway alterations in BRAF-mutant melanoma patients with acquired resistance to combined RAF/MEK inhibition. Cancer Discov. 2014 Jan;4(1):61-8.
|
| REF 3 |
BRAF inhibitor resistance mechanisms in metastatic melanoma: spectrum and clinical impact. Clin Cancer Res. 2014 Apr 1;20(7):1965-77.
|
| REF 4 |
ERK inhibition overcomes acquired resistance to MEK inhibitors. Mol Cancer Ther. 2012 May;11(5):1143-54.
|
| REF 5 |
Co-clinical assessment identifies patterns of BRAF inhibitor resistance in melanoma. J Clin Invest. 2015 Apr;125(4):1459-70.
|
| REF 6 |
Increased MAPK reactivation in early resistance to dabrafenib/trametinib combination therapy of BRAF-mutant metastatic melanoma. Nat Commun. 2014 Dec 2;5:5694.
|
