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 primary neoplasms 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
nt06234  cAMP signaling
nt06266  Non-small cell lung cancer
Gene
EML4-ALK (translocation) [HSA:238] [KO:K05119]
CD74-ROS1,SLC34A2-ROS1 (translocation) [HSA:6098] [KO:K05088]
KIF5B-RET (inversion) [HSA:5979] [KO:K05126]
RARB (promoter hypermethylation) [HSA:5915] [KO:K08528]
RASSF1 (promoter hypermethylation) [HSA:11186] [KO:K09850]
KRAS [HSA:3845] [KO:K07827]
EGFR [HSA:1956] [KO:K04361]
FHIT [HSA:2272] [KO:K01522]
CDKN2A [HSA:1029] [KO:K06621]
TP53 [HSA:7157] [KO:K04451]
MET [HSA:4233] [KO:K05099]
BRAF [HSA:673] [KO:K04365]
PIK3CA [HSA:5290] [KO:K00922]
IRF1 [HSA:3659] [KO:K09444]
PPP2R1B [HSA:5519] [KO:K03456]
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)
Selpercatinib [DR:D11713] (RET fusion positive)
Pralsetinib [DR:D11712] (RET fusion positive)
Necitumumab [DR:D10018]
Nivolumab [DR:D10316]
Pembrolizumab [DR:D10574] (PD-L1 expressed)
Durvalumab [DR:D10808]
Atezolizumab [DR:D10773]
Cemiplimab [DR:D11108]
Bevacizumab [DR:D06409]
Ramucirumab [DR:D09371]
Amivantamab [DR:D11894] (EGFR exon 20 insertion)
Sotorasib [DR:D12055] (KRAS G12C-mutated)
Mobocertinib succinate [DR:D11969] (EGFR exon 20 insertion mutation)
Other DBs
ICD-11: 2C25.0 2C25.2 2C25.3
ICD-10: C34
MeSH: D002289
Reference
  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
  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
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
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
PMID:17625570 (EML4-ALK translocation)
  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
PMID:19406209 (CD74-ROS1,SLC34A2-ROS1  translocation)
  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
PMID:22327623 (KIF5B-RET  inversion)
  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:18349282 (RARB promoter hypermethylation)
  Authors
Feng Q, Hawes SE, Stern JE, Wiens L, Lu H, Dong ZM, Jordan CD, Kiviat NB, Vesselle H
  Title
DNA methylation in tumor and matched normal tissues from non-small cell lung cancer patients.
  Journal
Cancer Epidemiol Biomarkers Prev 17:645-54 (2008)
DOI:10.1158/1055-9965.EPI-07-2518
Reference
PMID:11333291 (RASSF1 promoter hypermethylation)
  Authors
Burbee DG, Forgacs E, Zochbauer-Muller S, Shivakumar L, Fong K, Gao B, Randle D, Kondo M, Virmani A, Bader S, Sekido Y, Latif F, Milchgrub S, Toyooka S, Gazdar AF, Lerman MI, Zabarovsky E, White M, Minna JD
  Title
Epigenetic inactivation of RASSF1A in lung and breast cancers and malignant phenotype suppression.
  Journal
J Natl Cancer Inst 93:691-9 (2001)
DOI:10.1093/jnci/93.9.691
Reference
PMID:16533793 (KRAS)
  Authors
Tam IY, Chung LP, Suen WS, Wang E, Wong MC, Ho KK, Lam WK, Chiu SW, Girard L, Minna JD, Gazdar AF, Wong MP
  Title
Distinct epidermal growth factor receptor and KRAS mutation patterns in non-small cell lung cancer patients with different tobacco exposure and clinicopathologic features.
  Journal
Clin Cancer Res 12:1647-53 (2006)
DOI:10.1158/1078-0432.CCR-05-1981
Reference
PMID:15118073 (EGFR)
  Authors
Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, Harris PL, Haserlat SM, Supko JG, Haluska FG, Louis DN, Christiani DC, Settleman J, Haber DA.
  Title
Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib.
  Journal
N Engl J Med 350:2129-39 (2004)
DOI:10.1056/NEJMoa040938
Reference
PMID:8620533 (FHIT)
  Authors
Sozzi G, Veronese ML, Negrini M, Baffa R, Cotticelli MG, Inoue H, Tornielli S, Pilotti S, De Gregorio L, Pastorino U, Pierotti MA, Ohta M, Huebner K, Croce CM
  Title
The FHIT gene 3p14.2 is abnormal in lung cancer.
  Journal
Cell 85:17-26 (1996)
DOI:10.1016/s0092-8674(00)81078-8
Reference
PMID:8060323 (CDKN2A)
  Authors
Hayashi N, Sugimoto Y, Tsuchiya E, Ogawa M, Nakamura Y
  Title
Somatic mutations of the MTS (multiple tumor suppressor) 1/CDK4l (cyclin-dependent kinase-4 inhibitor) gene in human primary non-small cell lung carcinomas.
  Journal
Biochem Biophys Res Commun 202:1426-30 (1994)
DOI:10.1006/bbrc.1994.2090
Reference
PMID:2554494 (TP53)
  Authors
Takahashi T, Nau MM, Chiba I, Birrer MJ, Rosenberg RK, Vinocour M, Levitt M, Pass H, Gazdar AF, Minna JD
  Title
p53: a frequent target for genetic abnormalities in lung cancer.
  Journal
Science 246:491-4 (1989)
DOI:10.1126/science.2554494
Reference
PMID:28502721 (MET)
  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
Reference
PMID:12460918 (BRAF)
  Authors
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
  Title
BRAF and RAS mutations in human lung cancer and melanoma.
  Journal
Cancer Res 62:6997-7000 (2002)
Reference
PMID:15608678 (PIK3CA)
  Authors
Lee JW, Soung YH, Kim SY, Lee HW, Park WS, Nam SW, Kim SH, Lee JY, Yoo NJ, Lee SH
  Title
PIK3CA gene is frequently mutated in breast carcinomas and hepatocellular carcinomas.
  Journal
Oncogene 24:1477-80 (2005)
DOI:10.1038/sj.onc.1208304
Reference
PMID:10395927 (IRF1)
  Authors
Eason DD, Shepherd AT, Blanck G
  Title
Interferon regulatory factor 1 tryptophan 11 to arginine point mutation abolishes DNA binding.
  Journal
Biochim Biophys Acta 1446:140-4 (1999)
DOI:10.1016/s0167-4781(99)00078-0
Reference
PMID:9765152 (PPP2R1B)
  Authors
Wang SS, Esplin ED, Li JL, Huang L, Gazdar A, Minna J, Evans GA
  Title
Alterations of the PPP2R1B gene in human lung and colon cancer.
  Journal
Science 282:284-7 (1998)
DOI:10.1126/science.282.5387.284

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