| H00014 | |
| H number | H00014 |
| Name | Non-small cell lung cancer |
| 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 DIS_PATHWAY hsa05223 Non-small cell lung cancer |
| Network | nt06266 Non-small cell lung cancer nt06530(H00014) PI3K signaling |
| 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] |
| Pathogen | - |
| Env factor | - |
| Carcinogen | - |
| 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) Mobocertinib succinate [DR:D11969] (EGFR exon 20 insertion mutation) 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) Tremelimumab [DR:D06657] Sotorasib [DR:D12055] (KRAS G12C-mutated) Adagrasib [DR:D12301] (KRAS G12C-mutated) |
| Comment | - |
| Other DBs | ICD-11: 2C25.0 2C25.2 2C25.3 ICD-10: C34 MeSH: D002289 |
| Reference | PMID:12741677 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 PMID:12711111 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 PMID:12407699 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 PMID:16112428 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 PMID:15769940 AUTHORS Meuwissen R, Berns A. TITLE Mouse models for human lung cancer. JOURNAL Genes Dev 19:643-64 (2005) DOI:10.1101/gad.1284505 PMID:21850578 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 PMID:23733083 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 PMID:28443282 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 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 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 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 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 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 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 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 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 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 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 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 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) 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 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 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 |