KEGG   DISEASE: 非小細胞肺癌
エントリ  
H00014                                                             

名称    
非小細胞肺癌
  上位グループ
固形腫瘍 [DS:H02421]
概要    
Lung cancer is a leading cause of cancer death among men and women in industrialized countries. Non-small-cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer and represents a heterogeneous group of cancers, consisting mainly of squamous cell (SCC), adeno (AC) and large-cell carcinoma. Molecular mechanisms altered in NSCLC include activation of oncogenes, such as K-RAS, EGFR and EML4-ALK, and inactivation of tumorsuppressor genes, such as p53, p16INK4a, RAR-beta, and RASSF1. Point mutations within the K-RAS gene inactivate GTPase activity and the p21-RAS protein continuously transmits growth signals to the nucleus. Mutations or overexpression of EGFR leads to a proliferative advantage. EML4-ALK fusion leads to constitutive ALK activation, which causes cell proliferation, invasion, and inhibition of apoptosis. Inactivating mutation of p53 can lead to more rapid proliferation and reduced apoptosis. The protein encoded by the p16INK4a inhibits formation of CDK-cyclin-D complexes by competitive binding of CDK4 and CDK6. Loss of p16INK4a expression is a common feature of NSCLC. RAR-beta is a nuclear receptor that bears vitamin-A-dependent transcriptional activity. RASSF1A is able to form heterodimers with Nore-1, an RAS effector. Therefore loss of RASSF1A might shift the balance of RAS activity towards a growth-promoting effect.
カテゴリ  
がん
階層分類  
ヒト疾患 [BR:jp08402]
 がん
  肺および胸膜のがん
   H00014  非小細胞肺癌
ICD-11 による疾患分類 [BR:jp08403]
 02 腫瘍
  悪性腫瘍, ただしリンパ, 造血, 中枢神経系または関連組織の原発腫瘍を除く
   悪性腫瘍, 原発性と確定または推定されるもの, 明示された部位のもの, ただしリンパ, 造血, 中枢神経系, 関連組織を除く
    中耳, 呼吸器または胸腔内臓器の悪性腫瘍
     2C25  気管支または肺の悪性腫瘍
      H00014  非小細胞肺癌
パスウェイ 
hsa05223  非小細胞肺癌
関連パスウェイ
hsa05200  Pathways in cancer
hsa05206  MicroRNAs in cancer
ネットワーク
nt06234  cAMP signaling
nt06266  Non-small cell lung cancer
  エレメント
N00007  EML4-ALK fusion kinase to RAS-ERK signaling pathway
N00008  RET fusion kinase to RAS-ERK signaling pathway
N00012  Mutation-activated KRAS/NRAS to ERK signaling pathway
N00014  Mutation-activated EGFR to RAS-ERK signaling pathway
N00022  ERBB2-overexpression to RAS-ERK signaling pathway
N00024  Mutation-activated EGFR to PLCG-ERK signaling pathway
N00025  EML4-ALK fusion kinase to PLCG-ERK signaling pathway
N00032  Mutation-activated KRAS/NRAS to PI3K signaling pathway
N00036  Mutation-activated EGFR to PI3K signaling pathway
N00041  EGFR-overexpression to RAS-ERK signaling pathway
N00047  EML4-ALK fusion kinase to PI3K signaling pathway
N00070  Mutation-inactivated p16(INK4a) to p16-cell cycle G1/S
N00097  Loss of RASSF1 to RAS-RASSF1 signaling pathway
N00105  EML4-ALK fusion kinase to Jak-STAT signaling pathway
N00115  Mutation-inactivated TP53 to transcription
N01062  Mutation-activated MET to RAS-ERK signaling pathway
N01063  Mutation-activated MET to PI3K signaling pathway
N01337  NNK/NNN to CHRNA7-E2F signaling pathway
N01339  NNK/NNN to PI3K signaling pathway
N01341  NNK/NNN to Jak-STAT signaling pathway
N01344  NNK/NNN to RAS-ERK signaling pathway
N01346  Nicotine/NNK to cAMP signaling pathway
N01348  Nicotine/NNK to PI3K signaling pathway
N01355  Arsenic to PI3K signaling pathway
N01365  TCDD to Ahr signaling pathway
N01366  BaP to Ahr signaling pathway
N01373  MeIQx to DNA adducts
N01374  BaP to DNA adducts
N01378  AFB1 to DNA adducts
N01379  NNK to DNA adducts
N01380  NNK to DNA adducts
N01381  NNK to DNA adducts
N01382  NNK to DNA adducts
N01387  SM to DNA adducts/cross-links
N01392  Arsenic to electron transfer in complex II
N01393  Arsenic to electron transfer in complex II
N01394  Arsenic to electron transfer in complex IV
N01395  Cadmium to electron transfer in complex III
N01401  Benzo[a]pyrenre to CYP-mediated metabolism
N01407  Metals to JNK signaling pathway
N01408  Metals to RAS-ERK signaling pathway
N01409  Metals to PI3K signaling pathway
N01410  Metals to NFKB signaling pathway
N01411  Metals to NFKB signaling pathway
N01412  Metals to HTF-1 signaling pathway
N01413  Metals to KEAP1-NRF2 signalig pathway
病因遺伝子 
K-ras (mutation) [HSA:3845] [KO:K07827]
EGFR (mutation) [HSA:1956] [KO:K04361]
RAR-beta (promoter hypermethylation) [HSA:5915] [KO:K08528]
FHIT (mutation) [HSA:2272] [KO:K01522]
RASSF1 (promoter hypermethylation) [HSA:11186] [KO:K09850]
p16/INK4A (mutation) [HSA:1029] [KO:K06621]
p53 (mutation/deletion) [HSA:7157] [KO:K04451]
EML4-ALK (translocation) [HSA:238] [KO:K05119]
KIF5B-RET (inversion) [HSA:5979] [KO:K05126]
CD74-ROS1,SLC34A2-ROS1 (translocation) [HSA:6098] [KO:K05088]
MET (mutation) [HSA:4233] [KO:K05099]
BRAF (mutation) [HSA:673] [KO:K04365]
PIK3CA (mutation) [HSA:5290] [KO:K00922]
IRF1(mutation) [HSA:3659] [KO:K09444]
PPP2R1B(mutation, deletion) [HSA:5519] [KO:K03456]
発癌物質  
Arsenic and arsenic compounds [CPD:C06269]
Arsenic in drinking-water
Asbestos [CPD:C16442]
Chromium[VI]
Mustard gas (Sulfur mustard)
Nickel compounds
Plutonium-239 and its decay products (may contain plutonium-240 and other isotopes), as aerosols
Radon-222 and its decay products
Silica, crystalline (inhaled in the form of quartz orcristobalite from occupational sources) [CPD:C16459]
Tobacco smoking and tobacco smoke
*Aluminium production
*Benzo[a]pyrene [CPD:C07535]
*Cadmium and cadmium compounds
*Chimney sweeping
*Coal gasification
*Coal-tar pitches [CPD:C16451]
*Coal-tars
*Coke production
*Furniture and cabinet making
*Haematite mining (underground) with exposure to radon
*Household combustion of coal, indoor emissions from
*Involuntary smoking (exposure to secondhand or environmental tobacco smoke)
*Iron and steel founding
*Mineral oils, untreated and mildly treated
*Painter (occupational exposure as a)
*Paving and roofing with coal-tar pitch
*Shale-oils [CPD:C16458]
*Soots
*Strong-inorganic-acid mists containing sulfuric acid
*Talc containing asbestiform fibres
*2,3,7,8-Tetrachlorodibenzo-para-dioxin
*X- and gamma-radiation
*: Although this is a risk factor for lung cancer in general, the strength of association with different histological tumor types is not well understood.
治療薬   
シクロホスファミド水和物 [DR:D00287]
ニムスチン塩酸塩 [DR:D01059]
フルオロウラシル [DR:D00584]
シタラビン [DR:D00168]
ゲムシタビン塩酸塩 [DR:D01155]
ペメトレキセドナトリウム水和物 [DR:D06503]
テガフール・ウラシル [DR:D02131]
テガフール・ギメラシル・オテラシルカリウム [DR:D06399]
マイトマイシンC [DR:D00208]
ブレオマイシン塩酸塩 [DR:D03229]
ペプロマイシン硫酸塩 [DR:D02063]
ドキソルビシン塩酸塩 [DR:D01275]
アクラルビシン塩酸塩 [DR:D01911]
アムルビシン塩酸塩 [DR:D07100]
ビンデシン硫酸塩 [DR:D01769]
ビノレルビン酒石酸塩 [DR:D01935]
パクリタキセル [DR:D00491]
ドセタキセル水和物 [DR:D02165]
ドセタキセル [DR:D07866]
イリノテカン塩酸塩水和物 [DR:D01061]
ゲフィチニブ [DR:D01977] (EGFR遺伝子変異陽性)
エルロチニブ塩酸塩 [DR:D04023] (EGFR遺伝子変異陽性)
アファチニブマレイン酸塩 [DR:D09733] (EGFR遺伝子変異陽性)
オシメルチニブメシル酸塩 [DR:D10766] (EGFR遺伝子変異陽性)
ダコミチニブ水和物 [DR:D10514] (EGFR遺伝子変異陽性)
ダブラフェニブメシル酸塩 [DR:D10104] (BRAF遺伝子変異陽性)
クリゾチニブ [DR:D09731] (ALKまたはROS1融合遺伝子陽性)
セリチニブ [DR:D10551] (ALK融合遺伝子陽性)
アレクチニブ塩酸塩 [DR:D10450] (ALK融合遺伝子陽性)
ブリグチニブ [DR:D10866] (ALK融合遺伝子陽性)
ロルラチニブ [DR:D11012] (ALK融合遺伝子陽性)
トラメチニブジメチルスルホキシド付加物 [DR:D10176] (BRAF遺伝子変異陽性)
エヌトレクチニブ [DR:D10926] (ROS1融合遺伝子陽性)
カプマチニブ塩酸塩水和物 [DR:D10891] (MET遺伝子エクソン14スキッピング変異陽性)
テポチニブ塩酸塩水和物 [DR:D11073] (MET遺伝子エクソン14スキッピング変異陽性)
シスプラチン [DR:D00275]
カルボプラチン [DR:D01363]
ベバシズマブ [DR:D06409]
イピリムマブ [DR:D04603]
ニボルマブ [DR:D10316]
ラムシルマブ [DR:D09371]
ネシツムマブ [DR:D10018]
デュルバルマブ [DR:D10808]
アテゾリズマブ [DR:D10773]
ネダプラチン [DR:D01416]
セルペルカチニブ [DR:D11713] (RET融合遺伝子陽性)
タラポルフィンナトリウム [DR:D01985]
ストレプトコックス・ピオゲネス(A群3型)Su株ペニシリン処理凍結乾燥粉末 [DR:D08756]
コメント  
ICD-O: 8140/3, Tumor type: Adenocarcinoma
ICD-O: 8070/3, Tumor type: Squamous cell carcinoma
リンク   
ICD-11: 2C25.0 2C25.2 2C25.3
ICD-10: C34
MeSH: D002289
文献    
PMID:12741677 (tumor type)
  著者
Yokota J, Nishioka M, Tani M, Kohno T.
  タイトル
Genetic alterations responsible for metastatic phenotypes of lung cancer cells.
  雑誌
Clin Exp Metastasis 20:189-93 (2003)
DOI:10.1023/a:1022978932215
文献    
PMID:12711111 (tumor type)
  著者
Sanchez-Cespedes M.
  タイトル
Dissecting the genetic alterations involved in lung carcinogenesis.
  雑誌
Lung Cancer 40:111-21 (2003)
DOI:10.1016/S0169-5002(03)00033-3
文献    
  著者
Mitsuuchi Y, Testa JR.
  タイトル
Cytogenetics and molecular genetics of lung cancer.
  雑誌
Am J Med Genet 115:183-8 (2002)
DOI:10.1002/ajmg.10692
文献    
  著者
Panani AD, Roussos C.
  タイトル
Cytogenetic and molecular aspects of lung cancer.
  雑誌
Cancer Lett 239:1-9 (2006)
DOI:10.1016/j.canlet.2005.06.030
文献    
  著者
Meuwissen R, Berns A.
  タイトル
Mouse models for human lung cancer.
  雑誌
Genes Dev 19:643-64 (2005)
DOI:10.1101/gad.1284505
文献    
  著者
Soda M, Choi YL, Enomoto M, Takada S, Yamashita Y, Ishikawa S, Fujiwara S, Watanabe H, Kurashina K, Hatanaka H, Bando M, Ohno S, Ishikawa Y, Aburatani H, Niki T, Sohara Y, Sugiyama Y, Mano H
  タイトル
Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer.
  雑誌
Nature 448:561-6 (2007)
DOI:10.1038/nature05945
文献    
  著者
Brenner JC, Chinnaiyan AM
  タイトル
Translocations in epithelial cancers.
  雑誌
Biochim Biophys Acta 1796:201-15 (2009)
DOI:10.1016/j.bbcan.2009.04.005
文献    
  著者
Toyooka S, Mitsudomi T, Soh J, Aokage K, Yamane M, Oto T, Kiura K, Miyoshi S
  タイトル
Molecular oncology of lung cancer.
  雑誌
Gen Thorac Cardiovasc Surg 59:527-37 (2011)
DOI:10.1007/s11748-010-0743-3
文献    
  著者
Koudelakova V, Kneblova M, Trojanec R, Drabek J, Hajduch M
  タイトル
Non-small cell lung cancer--genetic predictors.
  雑誌
Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 157:125-36 (2013)
DOI:10.5507/bp.2013.034
文献    
  著者
Takeuchi K, Soda M, Togashi Y, Suzuki R, Sakata S, Hatano S, Asaka R, Hamanaka W, Ninomiya H, Uehara H, Lim Choi Y, Satoh Y, Okumura S, Nakagawa K, Mano H, Ishikawa Y
  タイトル
RET, ROS1 and ALK fusions in lung cancer.
  雑誌
Nat Med 18:378-81 (2012)
DOI:10.1038/nm.2658
文献    
PMID:15322513 (carcinogen)
  著者
Boffetta P.
  タイトル
Epidemiology of environmental and occupational cancer.
  雑誌
Oncogene 23:6392-403 (2004)
DOI:10.1038/sj.onc.1207715
文献    
PMID:2831418 (carcinogen)
  著者
Adachi S, Takemoto K.
  タイトル
[Occupational lung cancer. A comparison between humans and experimental animals]
  雑誌
Sangyo Igaku 29:345-57 (1987)
DOI:10.1539/joh1959.29.345
文献    
PMID:14643412 (carcinogen)
  著者
Rossman TG.
  タイトル
Mechanism of arsenic carcinogenesis: an integrated approach.
  雑誌
Mutat Res 533:37-65 (2003)
DOI:10.1016/j.mrfmmm.2003.07.009
文献    
PMID:17244035 (carcinogen)
  著者
Walvekar RR, Kane SV, Nadkarni MS, Bagwan IN, Chaukar DA, D'Cruz AK.
  タイトル
Chronic arsenic poisoning: a global health issue -- a report of multiple primary cancers.
  雑誌
J Cutan Pathol 34:203-6 (2007)
DOI:10.1111/j.1600-0560.2006.00596.x
文献    
PMID:15660110 (carcinogen)
  著者
Luch A.
  タイトル
Nature and nurture - lessons from chemical carcinogenesis.
  雑誌
Nat Rev Cancer 5:113-25 (2005)
DOI:10.1038/nrc1546
文献    
PMID:17375514 (carcinogen)
  著者
O'Reilly KM, Mclaughlin AM, Beckett WS, Sime PJ.
  タイトル
Asbestos-related lung disease.
  雑誌
Am Fam Physician 75:683-8 (2007)
文献    
PMID:12082370 (carcinogen)
  著者
Gottschall EB.
  タイトル
Occupational and environmental thoracic malignancies.
  雑誌
J Thorac Imaging 17:189-97 (2002)
DOI:10.1097/00005382-200207000-00003
文献    
PMID:12556326 (carcinogen)
  著者
Harrison JD, Muirhead CR.
  タイトル
Quantitative comparisons of cancer induction in humans by internally deposited radionuclides and external radiation.
  雑誌
Int J Radiat Biol 79:1-13 (2003)
DOI:10.1080/0955300021000038671
文献    
PMID:16411224 (carcinogen)
  著者
Taeger D, Fritsch A, Wiethege T, Johnen G, Eisenmenger A, Wesch H, Ko Y, Stier S, Michael Muller K, Bruning T, Pesch B.
  タイトル
Role of exposure to radon and silicosis on the cell type of lung carcinoma in German uranium miners.
  雑誌
Cancer 106:881-9 (2006)
DOI:10.1002/cncr.21677
文献    
PMID:11135223 (carcinogen)
  著者
Kreuzer M, Muller KM, Brachner A, Gerken M, Grosche B, Wiethege T, Wichmann HE.
  タイトル
Histopathologic findings of lung carcinoma in German uranium miners.
  雑誌
文献    
PMID:11886955 (carcinogen)
  著者
Verma DK, Purdham JT, Roels HA.
  タイトル
Translating evidence about occupational conditions into strategies for prevention.
  雑誌
Occup Environ Med 59:205-13; quiz 214 (2002)
DOI:10.1136/oem.59.3.156
文献    
PMID:9358915 (carcinogen)
  著者
Honma K, Chiyotani K, Kimura K.
  タイトル
Silicosis, mixed dust pneumoconiosis, and lung cancer.
  雑誌
文献    
PMID:15489140 (carcinogen)
  著者
Wogan GN, Hecht SS, Felton JS, Conney AH, Loeb LA.
  タイトル
Environmental and chemical carcinogenesis.
  雑誌
Semin Cancer Biol 14:473-86 (2004)
DOI:10.1016/j.semcancer.2004.06.010
文献    
PMID:15552776 (carcinogen)
  著者
Sasco AJ, Secretan MB, Straif K.
  タイトル
Tobacco smoking and cancer: a brief review of recent epidemiological evidence.
  雑誌
Lung Cancer 45 Suppl 2:S3-9 (2004)
DOI:10.1016/j.lungcan.2004.07.998
文献    
PMID:9498904 (carcinogen)
  著者
Boffetta P, Jourenkova N, Gustavsson P.
  タイトル
Cancer risk from occupational and environmental exposure to polycyclic aromatic hydrocarbons.
  雑誌
Cancer Causes Control 8:444-72 (1997)
DOI:10.1023/a:1018465507029
文献    
PMID:17530489 (carcinogen)
  著者
Abnet CC.
  タイトル
Carcinogenic food contaminants.
  雑誌
Cancer Invest 25:189-96 (2007)
DOI:10.1080/07357900701208733
文献    
PMID:17589590 (carcinogen)
  著者
Zhang JJ, Smith KR.
  タイトル
Household air pollution from coal and biomass fuels in china: measurements, health impacts, and interventions.
  雑誌
Environ Health Perspect 115:848-55 (2007)
DOI:10.1289/ehp.9479
文献    
PMID:17882278 (carcinogen)
  著者
Sun S, Schiller JH, Gazdar AF.
  タイトル
Lung cancer in never smokers--a different disease.
  雑誌
Nat Rev Cancer 7:778-90 (2007)
DOI:10.1038/nrc2190
文献    
PMID:10723042 (carcinogen)
  著者
Stern FB, Ruder AM, Chen G.
  タイトル
Proportionate mortality among unionized roofers and waterproofers.
  雑誌
文献    
PMID:17032693 (carcinogen)
  著者
Hsu YM, Wu CY, Lundgren DA, Birky BK.
  タイトル
Size-resolved sulfuric acid mist concentrations at phosphate fertilizer manufacturing facilities in Florida.
  雑誌
Ann Occup Hyg 51:81-9 (2007)
DOI:10.1093/annhyg/mel066
文献    
PMID:9498905 (carcinogen)
  著者
Blair A, Kazerouni N.
  タイトル
Reactive chemicals and cancer.
  雑誌
Cancer Causes Control 8:473-90 (1997)
DOI:10.1023/a:1018417623867
文献    
PMID:15070562 (carcinogen)
  著者
Berrington de Gonzalez A, Darby S.
  タイトル
Risk of cancer from diagnostic X-rays: estimates for the UK and 14 other countries.
  雑誌
Lancet 363:345-51 (2004)
DOI:10.1016/S0140-6736(04)15433-0
文献    
  著者
Sundar R, Chenard-Poirier M, Collins DC, Yap TA
  タイトル
Imprecision in the Era of Precision Medicine in Non-Small Cell Lung Cancer.
  雑誌
Front Med (Lausanne) 4:39 (2017)
DOI:10.3389/fmed.2017.00039
文献    
  著者
Lee GD, Lee SE, Oh DY, Yu DB, Jeong HM, Kim J, Hong S, Jung HS, Oh E, Song JY, Lee MS, Kim M, Jung K, Kim J, Shin YK, Choi YL, Kim HR
  タイトル
MET Exon 14 Skipping Mutations in Lung Adenocarcinoma: Clinicopathologic Implications and Prognostic Values.
  雑誌
J Thorac Oncol 12:1233-1246 (2017)
DOI:10.1016/j.jtho.2017.04.031
文献    
  著者
Brose MS, Volpe P, Feldman M, Kumar M, Rishi I, Gerrero R, Einhorn E, Herlyn M, Minna J, Nicholson A, Roth JA, Albelda SM, Davies H, Cox C, Brignell G, Stephens P, Futreal PA, Wooster R, Stratton MR, Weber BL
  タイトル
BRAF and RAS mutations in human lung cancer and melanoma.
  雑誌
Cancer Res 62:6997-7000 (2002)
文献    
  著者
Lee JW, Soung YH, Kim SY, Lee HW, Park WS, Nam SW, Kim SH, Lee JY, Yoo NJ, Lee SH
  タイトル
PIK3CA gene is frequently mutated in breast carcinomas and hepatocellular carcinomas.
  雑誌
Oncogene 24:1477-80 (2005)
DOI:10.1038/sj.onc.1208304
文献    
  著者
Eason DD, Shepherd AT, Blanck G
  タイトル
Interferon regulatory factor 1 tryptophan 11 to arginine point mutation abolishes DNA binding.
  雑誌
Biochim Biophys Acta 1446:140-4 (1999)
DOI:10.1016/s0167-4781(99)00078-0
文献    
PMID:9765152
  著者
Wang SS, Esplin ED, Li JL, Huang L, Gazdar A, Minna J, Evans GA
  タイトル
Alterations of the PPP2R1B gene in human lung and colon cancer.
  雑誌
Science 282:284-7 (1998)
DOI:10.1126/science.282.5387.284
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