Entry |
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Name |
Non-small cell lung cancer |
Supergrp |
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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.
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Category |
Cancer
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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
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Pathway |
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Network |
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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 |
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Gene |
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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.
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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]
Pralsetinib [DR: D11712] (RET fusion positive)
Selpercatinib [DR: D11713] (RET fusion positive)
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Comment |
ICD-O: 8140/3, Tumor type: Adenocarcinoma
ICD-O: 8070/3, Tumor type: Squamous cell carcinoma
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Other DBs |
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Reference |
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Authors |
Yokota J, Nishioka M, Tani M, Kohno T. |
Title |
Genetic alterations responsible for metastatic phenotypes of lung cancer cells. |
Journal |
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Reference |
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Authors |
Sanchez-Cespedes M. |
Title |
Dissecting the genetic alterations involved in lung carcinogenesis. |
Journal |
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Reference |
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Authors |
Mitsuuchi Y, Testa JR. |
Title |
Cytogenetics and molecular genetics of lung cancer. |
Journal |
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Reference |
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Authors |
Panani AD, Roussos C. |
Title |
Cytogenetic and molecular aspects of lung cancer. |
Journal |
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Reference |
|
Authors |
Meuwissen R, Berns A. |
Title |
Mouse models for human lung cancer. |
Journal |
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Reference |
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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 |
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Reference |
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Authors |
Brenner JC, Chinnaiyan AM |
Title |
Translocations in epithelial cancers. |
Journal |
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Reference |
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Authors |
Toyooka S, Mitsudomi T, Soh J, Aokage K, Yamane M, Oto T, Kiura K, Miyoshi S |
Title |
Molecular oncology of lung cancer. |
Journal |
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Reference |
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Authors |
Koudelakova V, Kneblova M, Trojanec R, Drabek J, Hajduch M |
Title |
Non-small cell lung cancer--genetic predictors. |
Journal |
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Reference |
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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 |
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Reference |
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Authors |
Boffetta P. |
Title |
Epidemiology of environmental and occupational cancer. |
Journal |
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Reference |
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Authors |
Adachi S, Takemoto K. |
Title |
[Occupational lung cancer. A comparison between humans and experimental animals] |
Journal |
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Reference |
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Authors |
Rossman TG. |
Title |
Mechanism of arsenic carcinogenesis: an integrated approach. |
Journal |
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Reference |
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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 |
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Reference |
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Authors |
Luch A. |
Title |
Nature and nurture - lessons from chemical carcinogenesis. |
Journal |
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Reference |
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Authors |
O'Reilly KM, Mclaughlin AM, Beckett WS, Sime PJ. |
Title |
Asbestos-related lung disease. |
Journal |
Am Fam Physician 75:683-8 (2007) |
Reference |
|
Authors |
Gottschall EB. |
Title |
Occupational and environmental thoracic malignancies. |
Journal |
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Reference |
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Authors |
Harrison JD, Muirhead CR. |
Title |
Quantitative comparisons of cancer induction in humans by internally deposited radionuclides and external radiation. |
Journal |
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Reference |
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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 |
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Reference |
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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 |
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Reference |
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Authors |
Verma DK, Purdham JT, Roels HA. |
Title |
Translating evidence about occupational conditions into strategies for prevention. |
Journal |
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Reference |
|
Authors |
Honma K, Chiyotani K, Kimura K. |
Title |
Silicosis, mixed dust pneumoconiosis, and lung cancer. |
Journal |
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Reference |
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Authors |
Wogan GN, Hecht SS, Felton JS, Conney AH, Loeb LA. |
Title |
Environmental and chemical carcinogenesis. |
Journal |
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Reference |
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Authors |
Sasco AJ, Secretan MB, Straif K. |
Title |
Tobacco smoking and cancer: a brief review of recent epidemiological evidence. |
Journal |
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Reference |
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Authors |
Boffetta P, Jourenkova N, Gustavsson P. |
Title |
Cancer risk from occupational and environmental exposure to polycyclic aromatic hydrocarbons. |
Journal |
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Reference |
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Authors |
Abnet CC. |
Title |
Carcinogenic food contaminants. |
Journal |
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Reference |
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Authors |
Zhang JJ, Smith KR. |
Title |
Household air pollution from coal and biomass fuels in china: measurements, health impacts, and interventions. |
Journal |
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Reference |
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Authors |
Sun S, Schiller JH, Gazdar AF. |
Title |
Lung cancer in never smokers--a different disease. |
Journal |
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Reference |
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Authors |
Stern FB, Ruder AM, Chen G. |
Title |
Proportionate mortality among unionized roofers and waterproofers. |
Journal |
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Reference |
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Authors |
Hsu YM, Wu CY, Lundgren DA, Birky BK. |
Title |
Size-resolved sulfuric acid mist concentrations at phosphate fertilizer manufacturing facilities in Florida. |
Journal |
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Reference |
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Authors |
Blair A, Kazerouni N. |
Title |
Reactive chemicals and cancer. |
Journal |
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Reference |
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Authors |
Berrington de Gonzalez A, Darby S. |
Title |
Risk of cancer from diagnostic X-rays: estimates for the UK and 14 other countries. |
Journal |
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Reference |
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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 |
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Reference |
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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 |
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LinkDB |
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