Non-small cell lung cancer

Solid tumor [DS:H02421]

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.

Cancer

nt06266  Non-small cell lung cancer

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]

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.

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]
Pralsetinib [DR:D11712] (RET fusion positive)
Selpercatinib [DR:D11713] (RET fusion positive)

ICD-O: 8140/3, Tumor type: Adenocarcinoma
ICD-O: 8070/3, Tumor type: Squamous cell carcinoma

PMID:12741677 (tumor type)

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Genetic alterations responsible for metastatic phenotypes of lung cancer cells.

Clin Exp Metastasis 20:189-93 (2003)
DOI:10.1023/a:1022978932215

PMID:12711111 (tumor type)

Sanchez-Cespedes M.

Dissecting the genetic alterations involved in lung carcinogenesis.

Lung Cancer 40:111-21 (2003)
DOI:10.1016/S0169-5002(03)00033-3

PMID:12407699

Mitsuuchi Y, Testa JR.

Cytogenetics and molecular genetics of lung cancer.

Am J Med Genet 115:183-8 (2002)
DOI:10.1002/ajmg.10692

PMID:16112428

Panani AD, Roussos C.

Cytogenetic and molecular aspects of lung cancer.

Cancer Lett 239:1-9 (2006)
DOI:10.1016/j.canlet.2005.06.030

PMID:15769940

Meuwissen R, Berns A.

Mouse models for human lung cancer.

Genes Dev 19:643-64 (2005)
DOI:10.1101/gad.1284505

PMID:17625570

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

Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer.

Nature 448:561-6 (2007)
DOI:10.1038/nature05945

PMID:19406209

Brenner JC, Chinnaiyan AM

Translocations in epithelial cancers.

Biochim Biophys Acta 1796:201-15 (2009)
DOI:10.1016/j.bbcan.2009.04.005

PMID:21850578

Toyooka S, Mitsudomi T, Soh J, Aokage K, Yamane M, Oto T, Kiura K, Miyoshi S

Molecular oncology of lung cancer.

Gen Thorac Cardiovasc Surg 59:527-37 (2011)
DOI:10.1007/s11748-010-0743-3

PMID:23733083

Koudelakova V, Kneblova M, Trojanec R, Drabek J, Hajduch M

Non-small cell lung cancer--genetic predictors.

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 157:125-36 (2013)
DOI:10.5507/bp.2013.034

PMID:22327623

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

RET, ROS1 and ALK fusions in lung cancer.

Nat Med 18:378-81 (2012)
DOI:10.1038/nm.2658

PMID:15322513 (carcinogen)

Boffetta P.

Epidemiology of environmental and occupational cancer.

Oncogene 23:6392-403 (2004)
DOI:10.1038/sj.onc.1207715

PMID:2831418 (carcinogen)

Adachi S, Takemoto K.

[Occupational lung cancer. A comparison between humans and experimental animals]

Sangyo Igaku 29:345-57 (1987)
DOI:10.1539/joh1959.29.345

PMID:14643412 (carcinogen)

Rossman TG.

Mechanism of arsenic carcinogenesis: an integrated approach.

Mutat Res 533:37-65 (2003)
DOI:10.1016/j.mrfmmm.2003.07.009

PMID:17244035 (carcinogen)

Walvekar RR, Kane SV, Nadkarni MS, Bagwan IN, Chaukar DA, D'Cruz AK.

Chronic arsenic poisoning: a global health issue -- a report of multiple primary cancers.

J Cutan Pathol 34:203-6 (2007)
DOI:10.1111/j.1600-0560.2006.00596.x

PMID:15660110 (carcinogen)

Luch A.

Nature and nurture - lessons from chemical carcinogenesis.

Nat Rev Cancer 5:113-25 (2005)
DOI:10.1038/nrc1546

PMID:17375514 (carcinogen)

O'Reilly KM, Mclaughlin AM, Beckett WS, Sime PJ.

Asbestos-related lung disease.

Am Fam Physician 75:683-8 (2007)

PMID:12082370 (carcinogen)

Gottschall EB.

Occupational and environmental thoracic malignancies.

J Thorac Imaging 17:189-97 (2002)
DOI:10.1097/00005382-200207000-00003

PMID:12556326 (carcinogen)

Harrison JD, Muirhead CR.

Quantitative comparisons of cancer induction in humans by internally deposited radionuclides and external radiation.

Int J Radiat Biol 79:1-13 (2003)
DOI:10.1080/0955300021000038671

PMID:16411224 (carcinogen)

Taeger D, Fritsch A, Wiethege T, Johnen G, Eisenmenger A, Wesch H, Ko Y, Stier S, Michael Muller K, Bruning T, Pesch B.

Role of exposure to radon and silicosis on the cell type of lung carcinoma in German uranium miners.

Cancer 106:881-9 (2006)
DOI:10.1002/cncr.21677

PMID:11135223 (carcinogen)

Kreuzer M, Muller KM, Brachner A, Gerken M, Grosche B, Wiethege T, Wichmann HE.

Histopathologic findings of lung carcinoma in German uranium miners.

Cancer 89:2613-21 (2000)
DOI:10.1002/1097-0142(20001215)89:12<2613::AID-CNCR14>3.0.CO;2-Y

PMID:11886955 (carcinogen)

Verma DK, Purdham JT, Roels HA.

Translating evidence about occupational conditions into strategies for prevention.

Occup Environ Med 59:205-13; quiz 214 (2002)
DOI:10.1136/oem.59.3.156

PMID:9358915 (carcinogen)

Honma K, Chiyotani K, Kimura K.

Silicosis, mixed dust pneumoconiosis, and lung cancer.

Am J Ind Med 32:595-9 (1997)
DOI:10.1002/(SICI)1097-0274(199712)32:6<595::AID-AJIM4>3.0.CO;2-P

PMID:15489140 (carcinogen)

Wogan GN, Hecht SS, Felton JS, Conney AH, Loeb LA.

Environmental and chemical carcinogenesis.

Semin Cancer Biol 14:473-86 (2004)
DOI:10.1016/j.semcancer.2004.06.010

PMID:15552776 (carcinogen)

Sasco AJ, Secretan MB, Straif K.

Tobacco smoking and cancer: a brief review of recent epidemiological evidence.

Lung Cancer 45 Suppl 2:S3-9 (2004)
DOI:10.1016/j.lungcan.2004.07.998

PMID:9498904 (carcinogen)

Boffetta P, Jourenkova N, Gustavsson P.

Cancer risk from occupational and environmental exposure to polycyclic aromatic hydrocarbons.

Cancer Causes Control 8:444-72 (1997)
DOI:10.1023/a:1018465507029

PMID:17530489 (carcinogen)

Abnet CC.

Carcinogenic food contaminants.

Cancer Invest 25:189-96 (2007)
DOI:10.1080/07357900701208733

PMID:17589590 (carcinogen)

Zhang JJ, Smith KR.

Household air pollution from coal and biomass fuels in china: measurements, health impacts, and interventions.

Environ Health Perspect 115:848-55 (2007)
DOI:10.1289/ehp.9479

PMID:17882278 (carcinogen)

Sun S, Schiller JH, Gazdar AF.

Lung cancer in never smokers--a different disease.

Nat Rev Cancer 7:778-90 (2007)
DOI:10.1038/nrc2190

PMID:10723042 (carcinogen)

Stern FB, Ruder AM, Chen G.

Proportionate mortality among unionized roofers and waterproofers.

Am J Ind Med 37:478-92 (2000)
DOI:10.1002/(SICI)1097-0274(200005)37:5<478::AID-AJIM4>3.0.CO;2-8

PMID:17032693 (carcinogen)

Hsu YM, Wu CY, Lundgren DA, Birky BK.

Size-resolved sulfuric acid mist concentrations at phosphate fertilizer manufacturing facilities in Florida.

Ann Occup Hyg 51:81-9 (2007)
DOI:10.1093/annhyg/mel066

PMID:9498905 (carcinogen)

Blair A, Kazerouni N.

Reactive chemicals and cancer.

Cancer Causes Control 8:473-90 (1997)
DOI:10.1023/a:1018417623867

PMID:15070562 (carcinogen)

Berrington de Gonzalez A, Darby S.

Risk of cancer from diagnostic X-rays: estimates for the UK and 14 other countries.

Lancet 363:345-51 (2004)
DOI:10.1016/S0140-6736(04)15433-0

PMID:28443282

Sundar R, Chenard-Poirier M, Collins DC, Yap TA

Imprecision in the Era of Precision Medicine in Non-Small Cell Lung Cancer.

Front Med (Lausanne) 4:39 (2017)
DOI:10.3389/fmed.2017.00039

PMID:28502721

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

MET Exon 14 Skipping Mutations in Lung Adenocarcinoma: Clinicopathologic Implications and Prognostic Values.

J Thorac Oncol 12:1233-1246 (2017)
DOI:10.1016/j.jtho.2017.04.031