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
NETWORK     nt06210  ERK signaling
            nt06215  WNT signaling
            nt06240  Transcription
            nt06260  Colorectal cancer
            nt06261  Gastric cancer
            nt06262  Pancreatic cancer
            nt06263  Hepatocellular carcinoma
            nt06265  Bladder cancer
            nt06266  Non-small cell lung cancer
            nt06267  Small cell lung cancer
            nt06268  Melanoma
            nt06269  Basal cell carcinoma
            nt06270  Breast cancer
            nt06271  Endometrial cancer
            nt06273  Glioma
            nt06274  Thyroid cancer
            nt06275  Acute myeloid leukemia
            nt06276  Chronic myeloid leukemia
  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   PMID:16557281
  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   PMID:16551846
  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   PMID:16946003
  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   PMID:17062879
  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   PMID:16242838
  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   PMID:16189702
  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   PMID:11165748
  AUTHORS   Gimm O.
  TITLE     Thyroid cancer.
  JOURNAL   Cancer Lett 163:143-56 (2001)
            DOI:10.1016/S0304-3835(00)00697-2
REFERENCE   PMID:12094241
  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
REL_PATHWAY hsa03320  PPAR signaling pathway
            hsa04010  MAPK signaling pathway
            hsa04115  p53 signaling pathway
            hsa04310  Wnt signaling pathway
            hsa04520  Adherens junction
KO_PATHWAY  ko05216
///
