KEGG   DISEASE: Non-small cell lung cancer
Entry
H00014                      Disease                                

Name
Non-small cell lung cancer
  Supergrp
Solid tumor [DS:H02421]
Description
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.
Category
Cancer
Brite
Human diseases [BR:br08402]
 Cancers
  Cancers of the lung and pleura
   H00014  Non-small cell lung cancer
Human diseases in ICD-11 classification [BR:br08403]
 02 Neoplasms
  Malignant neoplasms, except of lymphoid, haematopoietic, central nervous system or related tissues
   Malignant neoplasms, stated or presumed to be primary, of specified sites, except of lymphoid, haematopoietic, central nervous system or related tissues
    Malignant neoplasms of middle ear, respiratory or intrathoracic organs
     2C25  Malignant neoplasms of bronchus or lung
      H00014  Non-small cell lung cancer
Tumor markers [br08442.html]
 H00014
Cancer-associated carbohydrates [br08441.html]
 H00014
Pathway
hsa05223  Non-small cell lung cancer
Related
pathway
hsa05200  Pathways in cancer
hsa05206  MicroRNAs in cancer
Network
nt06266  Non-small cell lung cancer
  Element
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
Gene
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]
Carcinogen
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.
Drug
Methotrexate sodium [DR:D02115]
Pemetrexed sodium hydrate [DR:D06503]
Gemcitabine hydrochloride [DR:D01155]
Vinorelbine tartrate [DR:D01935]
Paclitaxel [DR:D00491]
Docetaxel [DR:D07866]
Docetaxel [DR:D02165]
Gefitinib [DR:D01977] (EGFR mutation positive)
Erlotinib hydrochloride [DR:D04023] (EGFR mutation positive)
Afatinib dimaleate [DR:D09733] (EGFR mutation positive)
Osimertinib mesylate [DR:D10766] (EGFR mutation positive)
Dacomitinib [DR:D10514] (EGFR mutation positive)
Dabrafenib mesylate [DR:D10104] (BRAF mutation positive)
Crizotinib [DR:D09731] (ALK or ROS1-positive)
Ceritinib [DR:D10551] (ALK positive)
Alectinib hydrochloride [DR:D10450] (ALK positive)
Brigatinib [DR:D10866] (ALK positive)
Lorlatinib [DR:D11012] (ALK positive)
Trametinib dimethyl sulfoxide [DR:D10176] (BRAF mutation positive)
Entrectinib [DR:D10926] (ROS1-positive)
Capmatinib hydrochloride [DR:D10891] (MET exon 14 skipping positive)
Tepotinib hydrochloride [DR:D11073] (MET exon 14 skipping)
Bevacizumab [DR:D06409]
Nivolumab [DR:D10316]
Pembrolizumab [DR:D10574] (PD-L1 expressed)
Ramucirumab [DR:D09371]
Necitumumab [DR:D10018]
Durvalumab [DR:D10808]
Atezolizumab [DR:D10773]
Cemiplimab [DR:D11108]
Pralsetinib [DR:D11712] (RET fusion positive)
Selpercatinib [DR:D11713] (RET fusion positive)
Comment
ICD-O: 8140/3, Tumor type: Adenocarcinoma
ICD-O: 8070/3, Tumor type: Squamous cell carcinoma
Other DBs
ICD-11: 2C25.0 2C25.2 2C25.3
ICD-10: C34
MeSH: D002289
Reference
PMID:12741677 (tumor type)
  Authors
Yokota J, Nishioka M, Tani M, Kohno T.
  Title
Genetic alterations responsible for metastatic phenotypes of lung cancer cells.
  Journal
Clin Exp Metastasis 20:189-93 (2003)
DOI:10.1023/a:1022978932215
Reference
PMID:12711111 (tumor type)
  Authors
Sanchez-Cespedes M.
  Title
Dissecting the genetic alterations involved in lung carcinogenesis.
  Journal
Lung Cancer 40:111-21 (2003)
DOI:10.1016/S0169-5002(03)00033-3
Reference
  Authors
Mitsuuchi Y, Testa JR.
  Title
Cytogenetics and molecular genetics of lung cancer.
  Journal
Am J Med Genet 115:183-8 (2002)
DOI:10.1002/ajmg.10692
Reference
  Authors
Panani AD, Roussos C.
  Title
Cytogenetic and molecular aspects of lung cancer.
  Journal
Cancer Lett 239:1-9 (2006)
DOI:10.1016/j.canlet.2005.06.030
Reference
  Authors
Meuwissen R, Berns A.
  Title
Mouse models for human lung cancer.
  Journal
Genes Dev 19:643-64 (2005)
DOI:10.1101/gad.1284505
Reference
  Authors
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
  Title
Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer.
  Journal
Nature 448:561-6 (2007)
DOI:10.1038/nature05945
Reference
  Authors
Brenner JC, Chinnaiyan AM
  Title
Translocations in epithelial cancers.
  Journal
Biochim Biophys Acta 1796:201-15 (2009)
DOI:10.1016/j.bbcan.2009.04.005
Reference
  Authors
Toyooka S, Mitsudomi T, Soh J, Aokage K, Yamane M, Oto T, Kiura K, Miyoshi S
  Title
Molecular oncology of lung cancer.
  Journal
Gen Thorac Cardiovasc Surg 59:527-37 (2011)
DOI:10.1007/s11748-010-0743-3
Reference
  Authors
Koudelakova V, Kneblova M, Trojanec R, Drabek J, Hajduch M
  Title
Non-small cell lung cancer--genetic predictors.
  Journal
Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 157:125-36 (2013)
DOI:10.5507/bp.2013.034
Reference
  Authors
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
  Title
RET, ROS1 and ALK fusions in lung cancer.
  Journal
Nat Med 18:378-81 (2012)
DOI:10.1038/nm.2658
Reference
PMID:15322513 (carcinogen)
  Authors
Boffetta P.
  Title
Epidemiology of environmental and occupational cancer.
  Journal
Oncogene 23:6392-403 (2004)
DOI:10.1038/sj.onc.1207715
Reference
PMID:2831418 (carcinogen)
  Authors
Adachi S, Takemoto K.
  Title
[Occupational lung cancer. A comparison between humans and experimental animals]
  Journal
Sangyo Igaku 29:345-57 (1987)
DOI:10.1539/joh1959.29.345
Reference
PMID:14643412 (carcinogen)
  Authors
Rossman TG.
  Title
Mechanism of arsenic carcinogenesis: an integrated approach.
  Journal
Mutat Res 533:37-65 (2003)
DOI:10.1016/j.mrfmmm.2003.07.009
Reference
PMID:17244035 (carcinogen)
  Authors
Walvekar RR, Kane SV, Nadkarni MS, Bagwan IN, Chaukar DA, D'Cruz AK.
  Title
Chronic arsenic poisoning: a global health issue -- a report of multiple primary cancers.
  Journal
J Cutan Pathol 34:203-6 (2007)
DOI:10.1111/j.1600-0560.2006.00596.x
Reference
PMID:15660110 (carcinogen)
  Authors
Luch A.
  Title
Nature and nurture - lessons from chemical carcinogenesis.
  Journal
Nat Rev Cancer 5:113-25 (2005)
DOI:10.1038/nrc1546
Reference
PMID:17375514 (carcinogen)
  Authors
O'Reilly KM, Mclaughlin AM, Beckett WS, Sime PJ.
  Title
Asbestos-related lung disease.
  Journal
Am Fam Physician 75:683-8 (2007)
Reference
PMID:12082370 (carcinogen)
  Authors
Gottschall EB.
  Title
Occupational and environmental thoracic malignancies.
  Journal
J Thorac Imaging 17:189-97 (2002)
DOI:10.1097/00005382-200207000-00003
Reference
PMID:12556326 (carcinogen)
  Authors
Harrison JD, Muirhead CR.
  Title
Quantitative comparisons of cancer induction in humans by internally deposited radionuclides and external radiation.
  Journal
Int J Radiat Biol 79:1-13 (2003)
DOI:10.1080/0955300021000038671
Reference
PMID:16411224 (carcinogen)
  Authors
Taeger D, Fritsch A, Wiethege T, Johnen G, Eisenmenger A, Wesch H, Ko Y, Stier S, Michael Muller K, Bruning T, Pesch B.
  Title
Role of exposure to radon and silicosis on the cell type of lung carcinoma in German uranium miners.
  Journal
Cancer 106:881-9 (2006)
DOI:10.1002/cncr.21677
Reference
PMID:11135223 (carcinogen)
  Authors
Kreuzer M, Muller KM, Brachner A, Gerken M, Grosche B, Wiethege T, Wichmann HE.
  Title
Histopathologic findings of lung carcinoma in German uranium miners.
  Journal
Reference
PMID:11886955 (carcinogen)
  Authors
Verma DK, Purdham JT, Roels HA.
  Title
Translating evidence about occupational conditions into strategies for prevention.
  Journal
Occup Environ Med 59:205-13; quiz 214 (2002)
DOI:10.1136/oem.59.3.156
Reference
PMID:9358915 (carcinogen)
  Authors
Honma K, Chiyotani K, Kimura K.
  Title
Silicosis, mixed dust pneumoconiosis, and lung cancer.
  Journal
Reference
PMID:15489140 (carcinogen)
  Authors
Wogan GN, Hecht SS, Felton JS, Conney AH, Loeb LA.
  Title
Environmental and chemical carcinogenesis.
  Journal
Semin Cancer Biol 14:473-86 (2004)
DOI:10.1016/j.semcancer.2004.06.010
Reference
PMID:15552776 (carcinogen)
  Authors
Sasco AJ, Secretan MB, Straif K.
  Title
Tobacco smoking and cancer: a brief review of recent epidemiological evidence.
  Journal
Lung Cancer 45 Suppl 2:S3-9 (2004)
DOI:10.1016/j.lungcan.2004.07.998
Reference
PMID:9498904 (carcinogen)
  Authors
Boffetta P, Jourenkova N, Gustavsson P.
  Title
Cancer risk from occupational and environmental exposure to polycyclic aromatic hydrocarbons.
  Journal
Cancer Causes Control 8:444-72 (1997)
DOI:10.1023/a:1018465507029
Reference
PMID:17530489 (carcinogen)
  Authors
Abnet CC.
  Title
Carcinogenic food contaminants.
  Journal
Cancer Invest 25:189-96 (2007)
DOI:10.1080/07357900701208733
Reference
PMID:17589590 (carcinogen)
  Authors
Zhang JJ, Smith KR.
  Title
Household air pollution from coal and biomass fuels in china: measurements, health impacts, and interventions.
  Journal
Environ Health Perspect 115:848-55 (2007)
DOI:10.1289/ehp.9479
Reference
PMID:17882278 (carcinogen)
  Authors
Sun S, Schiller JH, Gazdar AF.
  Title
Lung cancer in never smokers--a different disease.
  Journal
Nat Rev Cancer 7:778-90 (2007)
DOI:10.1038/nrc2190
Reference
PMID:10723042 (carcinogen)
  Authors
Stern FB, Ruder AM, Chen G.
  Title
Proportionate mortality among unionized roofers and waterproofers.
  Journal
Reference
PMID:17032693 (carcinogen)
  Authors
Hsu YM, Wu CY, Lundgren DA, Birky BK.
  Title
Size-resolved sulfuric acid mist concentrations at phosphate fertilizer manufacturing facilities in Florida.
  Journal
Ann Occup Hyg 51:81-9 (2007)
DOI:10.1093/annhyg/mel066
Reference
PMID:9498905 (carcinogen)
  Authors
Blair A, Kazerouni N.
  Title
Reactive chemicals and cancer.
  Journal
Cancer Causes Control 8:473-90 (1997)
DOI:10.1023/a:1018417623867
Reference
PMID:15070562 (carcinogen)
  Authors
Berrington de Gonzalez A, Darby S.
  Title
Risk of cancer from diagnostic X-rays: estimates for the UK and 14 other countries.
  Journal
Lancet 363:345-51 (2004)
DOI:10.1016/S0140-6736(04)15433-0
Reference
  Authors
Sundar R, Chenard-Poirier M, Collins DC, Yap TA
  Title
Imprecision in the Era of Precision Medicine in Non-Small Cell Lung Cancer.
  Journal
Front Med (Lausanne) 4:39 (2017)
DOI:10.3389/fmed.2017.00039
Reference
  Authors
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
  Title
MET Exon 14 Skipping Mutations in Lung Adenocarcinoma: Clinicopathologic Implications and Prognostic Values.
  Journal
J Thorac Oncol 12:1233-1246 (2017)
DOI:10.1016/j.jtho.2017.04.031

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Ontology (4)   
   KEGG BRITE (4)   
Pathway (2)   
   KEGG PATHWAY (2)   
Network (17)   
   KEGG NETWORK (17)   
Drug (53)   
   KEGG DRUG (53)   
Chemical substance (6)   
   KEGG COMPOUND (6)   
Gene (22)   
   KEGG ORTHOLOGY (11)   
   KEGG GENES (11)   
Literature (34)   
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