KEGG   PATHWAY: hsa05216
Entry
hsa05216                    Pathway                                
Name
Thyroid cancer - Homo sapiens (human)
Description
Thyroid cancer is the most common endocrine malignancy and accounts for the majority of endocrine cancer- related deaths each year. More than 95% of thyroid carcinomas are derived from follicular cells. Their behavior varies from the indolent growing, well-differentiated papillary and follicular carcinomas (PTC and FTC, respectively) to the extremely aggressive undifferentiated carcinoma (UC). Somatic rearrangements of RET and TRK are almost exclusively found in PTC and may be found in early stages. The most distinctive molecular features of FTC are the prominence of aneuploidy and the high prevalence of RAS mutations and PAX8-PPAR{gamma} rearrangements. p53 seems to play a crucial role in the dedifferentiation process of thyroid carcinoma.
Class
Human Diseases; Cancer: specific types
Pathway map
hsa05216  Thyroid cancer
hsa05216

Network
  Element
N00008  RET fusion kinase to RAS-ERK signaling pathway
N00009  TRK fusion kinase to RAS-ERK signaling pathway
N00012  Mutation-activated KRAS/NRAS to ERK signaling pathway
N00013  Mutation-activated BRAF to ERK signaling pathway
N00061  CDH1-reduced expression to beta-catenin signaling pathway
N00115  Mutation-inactivated TP53 to transcription
N00126  PAX8-PPARG fusion to PPARG-mediated transcription
Disease
H00032  Thyroid cancer
Drug
D06272  Sorafenib tosylate (USAN)
D06407  Vandetanib (JAN/USAN/INN)
D08524  Sorafenib (USAN/INN)
D09919  Lenvatinib (USAN/INN)
D09920  Lenvatinib mesylate (USAN)
D11713  Selpercatinib (JAN/USAN/INN)
Organism
Homo sapiens (human) [GN:hsa]
Gene
5979  RET; ret proto-oncogene [KO:K05126] [EC:2.7.10.1]
8030  CCDC6; coiled-coil domain containing 6 [KO:K09288]
8031  NCOA4; nuclear receptor coactivator 4 [KO:K09289]
4914  NTRK1; neurotrophic receptor tyrosine kinase 1 [KO:K03176] [EC:2.7.10.1]
7170  TPM3; tropomyosin 3 [KO:K09290]
7175  TPR; translocated promoter region, nuclear basket protein [KO:K09291]
10342  TFG; trafficking from ER to golgi regulator [KO:K09292]
3265  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
4893  NRAS; NRAS proto-oncogene, GTPase [KO:K07828]
3845  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
673  BRAF; B-Raf proto-oncogene, serine/threonine kinase [KO:K04365] [EC:2.7.11.1]
5604  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
5605  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
5594  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
5595  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
7849  PAX8; paired box 8 [KO:K09293]
5468  PPARG; peroxisome proliferator activated receptor gamma [KO:K08530]
6256  RXRA; retinoid X receptor alpha [KO:K08524]
6257  RXRB; retinoid X receptor beta [KO:K08525]
6258  RXRG; retinoid X receptor gamma [KO:K08526]
7157  TP53; tumor protein p53 [KO:K04451]
1026  CDKN1A; cyclin dependent kinase inhibitor 1A [KO:K06625]
1647  GADD45A; growth arrest and DNA damage inducible alpha [KO:K04402]
4616  GADD45B; growth arrest and DNA damage inducible beta [KO:K04402]
10912  GADD45G; growth arrest and DNA damage inducible gamma [KO:K04402]
581  BAX; BCL2 associated X, apoptosis regulator [KO:K02159]
578  BAK1; BCL2 antagonist/killer 1 [KO:K14021]
1643  DDB2; damage specific DNA binding protein 2 [KO:K10140]
51426  POLK; DNA polymerase kappa [KO:K03511] [EC:2.7.7.7]
999  CDH1; cadherin 1 [KO:K05689]
1499  CTNNB1; catenin beta 1 [KO:K02105]
6932  TCF7; transcription factor 7 [KO:K02620]
83439  TCF7L1; transcription factor 7 like 1 [KO:K04490]
6934  TCF7L2; transcription factor 7 like 2 [KO:K04491]
51176  LEF1; lymphoid enhancer binding factor 1 [KO:K04492]
4609  MYC; MYC proto-oncogene, bHLH transcription factor [KO:K04377]
595  CCND1; cyclin D1 [KO:K04503]
Reference
  Authors
Kondo T, Ezzat S, Asa SL.
  Title
Pathogenetic mechanisms in thyroid follicular-cell neoplasia.
  Journal
Nat Rev Cancer 6:292-306 (2006)
DOI:10.1038/nrc1836
Reference
  Authors
Chiloeches A, Marais R.
  Title
Is BRAF the Achilles' Heel of thyroid cancer?
  Journal
Clin Cancer Res 12:1661-4 (2006)
DOI:10.1158/1078-0432.CCR-06-0051
Reference
  Authors
Reddi HV, McIver B, Grebe SK, Eberhardt NL
  Title
The paired box-8/peroxisome proliferator-activated receptor-gamma oncogene in thyroid tumorigenesis.
  Journal
Endocrinology 148:932-5 (2007)
DOI:10.1210/en.2006-0926
Reference
  Authors
Santoro M, Melillo RM, Fusco A.
  Title
RET/PTC activation in papillary thyroid carcinoma: European Journal of Endocrinology Prize Lecture.
  Journal
Eur J Endocrinol 155:645-653 (2006)
DOI:10.1530/eje.1.02289
Reference
  Authors
Pierotti MA, Greco A.
  Title
Oncogenic rearrangements of the NTRK1/NGF receptor.
  Journal
Cancer Lett 232:90-8 (2006)
DOI:10.1016/j.canlet.2005.07.043
Reference
  Authors
Sobrinho-Simoes M, Preto A, Rocha AS, Castro P, Maximo V, Fonseca E, Soares P.
  Title
Molecular pathology of well-differentiated thyroid carcinomas.
  Journal
Virchows Arch 447:787-93 (2005)
DOI:10.1007/s00428-005-0065-5
Reference
  Authors
Gimm O.
  Title
Thyroid cancer.
  Journal
Cancer Lett 163:143-56 (2001)
DOI:10.1016/S0304-3835(00)00697-2
Reference
  Authors
Williams D.
  Title
Cancer after nuclear fallout: lessons from the Chernobyl accident.
  Journal
Nat Rev Cancer 2:543-9 (2002)
DOI:10.1038/nrc845
Related
pathway
hsa03320  PPAR signaling pathway
hsa04010  MAPK signaling pathway
hsa04115  p53 signaling pathway
hsa04310  Wnt signaling pathway
hsa04520  Adherens junction
KO pathway
ko05216   
LinkDB

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