Recurrent genetic alterations and targeted therapies under investigation in iCCA

Recurrent genetic alterations and targeted therapies under investigation in iCCA. Genetic alterations in tyrosine kinase receptors and downstream RAS/MAPK, PI3K/AKT/mTOR effector casades result in aberrant modulation of proliferation, apoptosis and cell cycle. Newly identified mutations in MAP3K4 lead to EMT process in iCCA through p38/NF-kB signaling pathway. Mutated IDH1/IDH2 result in the accumulation of oncogenic metabolite 2HG. Potential targeted therapies against the above alterations are currently under clinical trials. Recurrently mutated chromatin remodeling genes also present as druggable targets.
Recurrent genetic alterations and targeted therapies under investigation in iCCA
Download JPG
View figure at PMC Read paper at PMC Open at NDEx
PMC
NDEx

Publication

Genetic profiling of intrahepatic cholangiocarcinoma and its clinical implication in targeted therapy. (2016) Diyang Xie, et al. Am J Cancer Res. 2016;6(3):577-586. Figure: F1.

Gene mentions


Organism Group Word Match Source NCBI Symbol NCBI ID
Homo sapiens Primates ROS1 ROS1 ncbigene_symbol ROS1 6098
Homo sapiens Primates FGFR2 FGFR2 ncbigene_symbol FGFR2 2263
Homo sapiens Primates C-MET C-MET ncbigene_synonym MET 4233
Homo sapiens Primates EGF EGF ncbigene_symbol EGF 1950
Homo sapiens Primates EGFR EGFR ncbigene_symbol EGFR 1956
Homo sapiens Primates IDH1 IDH1 ncbigene_symbol IDH1 3417
Homo sapiens Primates TAG TAG ncbigene_synonym TMED7 51014
Homo sapiens Primates TAG TAG ncbigene_synonym LINC01194 404663
Homo sapiens Primates IDH2 IDH2 ncbigene_symbol IDH2 3418
Homo sapiens Primates PI3K/AKT/MTOR MTOR ncbigene_symbol MTOR 2475
Homo sapiens Primates PI3K/AKT/MTOR AKT ncbigene_synonym AKT1 207
Homo sapiens Primates PI3K/AKT/MTOR AKT famplex_relations AKT2 208
Homo sapiens Primates PI3K/AKT/MTOR AKT famplex_relations AKT3 10000
Homo sapiens Primates PI3K/AKT/MTOR PI3K ncbigene_synonym PIK3CA 5290
Homo sapiens Primates PI3K/AKT/MTOR PI3K ncbigene_synonym PIK3CB 5291
Homo sapiens Primates PI3K/AKT/MTOR PI3K ncbigene_synonym PIK3CD 5293
Homo sapiens Primates PI3K/AKT/MTOR PI3K ncbigene_synonym PIK3CG 5294
Homo sapiens Primates PI3K/AKT/MTOR PI3K famplex_relations PIK3R3 8503
Homo sapiens Primates PI3K/AKT/MTOR PI3K famplex_relations PIK3R4 30849
Homo sapiens Primates PI3K/AKT/MTOR PI3K famplex_relations PIK3R5 23533
Homo sapiens Primates PI3K/AKT/MTOR PI3K famplex_relations PIK3R6 146850
Homo sapiens Primates PI3K/AKT/MTOR PI3K famplex_relations PIK3R1 5295
Homo sapiens Primates PI3K/AKT/MTOR PI3K famplex_relations PIK3R2 5296
Homo sapiens Primates RAS/MAPK MAPK famplex_relations MAPK1 5594
Homo sapiens Primates RAS/MAPK MAPK famplex_relations MAPK3 5595
Homo sapiens Primates RAS/MAPK MAPK famplex_relations MAPK11 5600
Homo sapiens Primates RAS/MAPK MAPK famplex_relations MAPK12 6300
Homo sapiens Primates RAS/MAPK MAPK famplex_relations MAPK13 5603
Homo sapiens Primates RAS/MAPK MAPK famplex_relations MAPK14 1432
Homo sapiens Primates RAS/MAPK MAPK famplex_relations MAPK8 5599
Homo sapiens Primates RAS/MAPK MAPK famplex_relations MAPK9 5601
Homo sapiens Primates RAS/MAPK MAPK famplex_relations MAPK10 5602
Homo sapiens Primates RAS/MAPK RAS famplex_relations KRAS 3845
Homo sapiens Primates RAS/MAPK RAS famplex_relations HRAS 3265
Homo sapiens Primates RAS/MAPK RAS famplex_relations NRAS 4893
Homo sapiens Primates MAP3K4/p38 MAP3K4 ncbigene_symbol MAP3K4 4216
Homo sapiens Primates MAP3K4/p38 P38 ncbigene_synonym CRK 1398
Homo sapiens Primates MAP3K4/p38 P38 ncbigene_synonym AIMP2 7965
Homo sapiens Primates MAP3K4/p38 P38 ncbigene_synonym GRAP2 9402
Homo sapiens Primates MAP3K4/p38 P38 ncbigene_synonym AHSA1 10598
Homo sapiens Primates MAP3K4/p38 P38 ncbigene_synonym POLDIP2 26073
Homo sapiens Primates PTPN3 PTPN3 ncbigene_symbol PTPN3 5774
Homo sapiens Primates RAF RAF ncbigene_synonym ZHX2 22882
Homo sapiens Primates RAF RAF famplex_relations ARAF 369
Homo sapiens Primates RAF RAF famplex_relations BRAF 673
Homo sapiens Primates RAF RAF famplex_relations RAF1 5894
Homo sapiens Primates TP53,CDK6 CDK6 ncbigene_symbol CDK6 1021
Homo sapiens Primates TP53,CDK6 TP53 ncbigene_symbol TP53 7157
Homo sapiens Primates CCND1 CCND1 ncbigene_symbol CCND1 595
Homo sapiens Primates MEK MEK ncbigene_synonym MAP2K7 5609
Homo sapiens Primates MEK MEK famplex_relations MAP2K1 5604
Homo sapiens Primates MEK MEK famplex_relations MAP2K2 5605
Homo sapiens Primates NF-KB NF-KB ncbigene_synonym NFKB1 4790
Homo sapiens Primates ARID1A ARID1A ncbigene_symbol ARID1A 8289
Homo sapiens Primates PRRM1,BAP1 BAP1 ncbigene_symbol BAP1 8314
Homo sapiens Primates PRRM1,BAP1 BAP1 ncbigene_synonym RNF2 6045
Homo sapiens Primates PRRM1,BAP1 BAP1 ncbigene_synonym MAGI1 9223
Homo sapiens Primates ERK ERK ncbigene_synonym EPHB2 2048
Homo sapiens Primates EMT EMT ncbigene_synonym ITK 3702
Homo sapiens Primates EMT EMT ncbigene_synonym SLC22A3 6581

Chemical mentions

Word Match MeSH Name ChEBI
Cabozantinib cabozantinib mesh:C558660 cabozantinib chebi:72317
Regorafenib regorafenib mesh:C559147 regorafenib chebi:68647
Isocitrate NA mesh:D007523

Disease mentions

Word Match MeSH Name DOID
Cancer NA
Cardiomyopathy NA
Cholangiocarcinoma NA
Lung cancer NA
Melanoma NA
Noonan syndrome NA