| H00014 | |
| H番号 | H00014 |
| 名称 | 非小細胞肺癌 |
| 概要 | 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. |
| カテゴリ | がん 疾患パスウェイ hsa05223 非小細胞肺癌 |
| ネットワーク | nt06266 Non-small cell lung cancer nt06530(H00014) PI3K signaling |
| 病因遺伝子 | 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] |
| 病原体 | - |
| 環境要因 | - |
| 発癌物質 | - |
| 治療薬 | マイトマイシンC [DR:D00208] シクロホスファミド水和物 [DR:D00287] ニムスチン塩酸塩 [DR:D01059] フルオロウラシル [DR:D00584] シタラビン [DR:D00168] ゲムシタビン塩酸塩 [DR:D01155] ペメトレキセドナトリウム水和物 [DR:D06503] ペメトレキセドナトリウムヘミペンタ水和物 [DR:D10596] テガフール・ウラシル [DR:D02131] テガフール・ギメラシル・オテラシルカリウム [DR:D06399] ブレオマイシン塩酸塩 [DR:D03229] ペプロマイシン硫酸塩 [DR:D02063] ドキソルビシン塩酸塩 [DR:D01275] アクラルビシン塩酸塩 [DR:D01911] アムルビシン塩酸塩 [DR:D07100] ビンデシン硫酸塩 [DR:D01769] ビノレルビン酒石酸塩 [DR:D01935] パクリタキセル [DR:D00491] ドセタキセル水和物 [DR:D02165] ドセタキセル [DR:D07866] イリノテカン塩酸塩水和物 [DR:D01061] ゲフィチニブ [DR:D01977] (EGFR遺伝子変異陽性) エルロチニブ塩酸塩 [DR:D04023] (EGFR遺伝子変異陽性) アファチニブマレイン酸塩 [DR:D09733] (EGFR遺伝子変異陽性) オシメルチニブメシル酸塩 [DR:D10766] (EGFR遺伝子変異陽性) ダコミチニブ水和物 [DR:D10514] (EGFR遺伝子変異陽性) ダブラフェニブメシル酸塩 [DR:D10104] (BRAF遺伝子変異陽性) クリゾチニブ [DR:D09731] (ALKまたはROS1融合遺伝子陽性) セリチニブ [DR:D10551] (ALK融合遺伝子陽性) アレクチニブ塩酸塩 [DR:D10450] (ALK融合遺伝子陽性) ブリグチニブ [DR:D10866] (ALK融合遺伝子陽性) ロルラチニブ [DR:D11012] (ALK融合遺伝子陽性) トラメチニブジメチルスルホキシド付加物 [DR:D10176] (BRAF遺伝子変異陽性) エヌトレクチニブ [DR:D10926] (ROS1融合遺伝子陽性) カプマチニブ塩酸塩水和物 [DR:D10891] (MET遺伝子エクソン14スキッピング変異陽性) テポチニブ塩酸塩水和物 [DR:D11073] (MET遺伝子エクソン14スキッピング変異陽性) セルペルカチニブ [DR:D11713] (RET融合遺伝子陽性) トラスツズマブデルクステカン [DR:D11529] (HER2遺伝子変異陽性) ネシツムマブ [DR:D10018] ニボルマブ [DR:D10316] ペムブロリズマブ [DR:D10574] デュルバルマブ [DR:D10808] アテゾリズマブ [DR:D10773] (PD-L1陽性) ベバシズマブ [DR:D06409] ラムシルマブ [DR:D09371] イピリムマブ [DR:D04603] トレメリムマブ [DR:D06657] シスプラチン [DR:D00275] カルボプラチン [DR:D01363] ソトラシブ [DR:D12055] (KRAS G12C変異陽性) ネダプラチン [DR:D01416] タラポルフィンナトリウム [DR:D01985] ストレプトコックス・ピオゲネス（A群3型）Su株ペニシリン処理凍結乾燥粉末 [DR:D08756] |
| コメント | - |
| リンク | ICD-11: 2C25.0 2C25.2 2C25.3 ICD-10: C34 MeSH: D002289 |
| 文献 | PMID:12741677 著者 Yokota J, Nishioka M, Tani M, Kohno T. タイトル Genetic alterations responsible for metastatic phenotypes of lung cancer cells. 雑誌 Clin Exp Metastasis 20:189-93 (2003) DOI:10.1023/a:1022978932215 PMID:12711111 著者 Sanchez-Cespedes M. タイトル Dissecting the genetic alterations involved in lung carcinogenesis. 雑誌 Lung Cancer 40:111-21 (2003) DOI:10.1016/S0169-5002(03)00033-3 PMID:12407699 著者 Mitsuuchi Y, Testa JR. タイトル Cytogenetics and molecular genetics of lung cancer. 雑誌 Am J Med Genet 115:183-8 (2002) DOI:10.1002/ajmg.10692 PMID:16112428 著者 Panani AD, Roussos C. タイトル Cytogenetic and molecular aspects of lung cancer. 雑誌 Cancer Lett 239:1-9 (2006) DOI:10.1016/j.canlet.2005.06.030 PMID:15769940 著者 Meuwissen R, Berns A. タイトル Mouse models for human lung cancer. 雑誌 Genes Dev 19:643-64 (2005) DOI:10.1101/gad.1284505 PMID:21850578 著者 Toyooka S, Mitsudomi T, Soh J, Aokage K, Yamane M, Oto T, Kiura K, Miyoshi S タイトル Molecular oncology of lung cancer. 雑誌 Gen Thorac Cardiovasc Surg 59:527-37 (2011) DOI:10.1007/s11748-010-0743-3 PMID:23733083 著者 Koudelakova V, Kneblova M, Trojanec R, Drabek J, Hajduch M タイトル Non-small cell lung cancer--genetic predictors. 雑誌 Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 157:125-36 (2013) DOI:10.5507/bp.2013.034 PMID:28443282 著者 Sundar R, Chenard-Poirier M, Collins DC, Yap TA タイトル Imprecision in the Era of Precision Medicine in Non-Small Cell Lung Cancer. 雑誌 Front Med (Lausanne) 4:39 (2017) DOI:10.3389/fmed.2017.00039 PMID:17625570 (EML4-ALK translocation) 著者 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 タイトル Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. 雑誌 Nature 448:561-6 (2007) DOI:10.1038/nature05945 PMID:19406209 (CD74-ROS1,SLC34A2-ROS1 translocation) 著者 Brenner JC, Chinnaiyan AM タイトル Translocations in epithelial cancers. 雑誌 Biochim Biophys Acta 1796:201-15 (2009) DOI:10.1016/j.bbcan.2009.04.005 PMID:22327623 (KIF5B-RET inversion) 著者 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 タイトル RET, ROS1 and ALK fusions in lung cancer. 雑誌 Nat Med 18:378-81 (2012) DOI:10.1038/nm.2658 PMID:18349282 (RARB promoter hypermethylation) 著者 Feng Q, Hawes SE, Stern JE, Wiens L, Lu H, Dong ZM, Jordan CD, Kiviat NB, Vesselle H タイトル DNA methylation in tumor and matched normal tissues from non-small cell lung cancer patients. 雑誌 Cancer Epidemiol Biomarkers Prev 17:645-54 (2008) DOI:10.1158/1055-9965.EPI-07-2518 PMID:11333291 (RASSF1 promoter hypermethylation) 著者 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 タイトル Epigenetic inactivation of RASSF1A in lung and breast cancers and malignant phenotype suppression. 雑誌 J Natl Cancer Inst 93:691-9 (2001) DOI:10.1093/jnci/93.9.691 PMID:16533793 (KRAS) 著者 Tam IY, Chung LP, Suen WS, Wang E, Wong MC, Ho KK, Lam WK, Chiu SW, Girard L, Minna JD, Gazdar AF, Wong MP タイトル Distinct epidermal growth factor receptor and KRAS mutation patterns in non-small cell lung cancer patients with different tobacco exposure and clinicopathologic features. 雑誌 Clin Cancer Res 12:1647-53 (2006) DOI:10.1158/1078-0432.CCR-05-1981 PMID:15118073 (EGFR) 著者 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. タイトル Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. 雑誌 N Engl J Med 350:2129-39 (2004) DOI:10.1056/NEJMoa040938 PMID:8620533 (FHIT) 著者 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 タイトル The FHIT gene 3p14.2 is abnormal in lung cancer. 雑誌 Cell 85:17-26 (1996) DOI:10.1016/s0092-8674(00)81078-8 PMID:8060323 (CDKN2A) 著者 Hayashi N, Sugimoto Y, Tsuchiya E, Ogawa M, Nakamura Y タイトル Somatic mutations of the MTS (multiple tumor suppressor) 1/CDK4l (cyclin-dependent kinase-4 inhibitor) gene in human primary non-small cell lung carcinomas. 雑誌 Biochem Biophys Res Commun 202:1426-30 (1994) DOI:10.1006/bbrc.1994.2090 PMID:2554494 (TP53) 著者 Takahashi T, Nau MM, Chiba I, Birrer MJ, Rosenberg RK, Vinocour M, Levitt M, Pass H, Gazdar AF, Minna JD タイトル p53: a frequent target for genetic abnormalities in lung cancer. 雑誌 Science 246:491-4 (1989) DOI:10.1126/science.2554494 PMID:28502721 (MET) 著者 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 タイトル MET Exon 14 Skipping Mutations in Lung Adenocarcinoma: Clinicopathologic Implications and Prognostic Values. 雑誌 J Thorac Oncol 12:1233-1246 (2017) DOI:10.1016/j.jtho.2017.04.031 PMID:12460918 (BRAF) 著者 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 タイトル BRAF and RAS mutations in human lung cancer and melanoma. 雑誌 Cancer Res 62:6997-7000 (2002) PMID:15608678 (PIK3CA) 著者 Lee JW, Soung YH, Kim SY, Lee HW, Park WS, Nam SW, Kim SH, Lee JY, Yoo NJ, Lee SH タイトル PIK3CA gene is frequently mutated in breast carcinomas and hepatocellular carcinomas. 雑誌 Oncogene 24:1477-80 (2005) DOI:10.1038/sj.onc.1208304 PMID:10395927 (IRF1) 著者 Eason DD, Shepherd AT, Blanck G タイトル Interferon regulatory factor 1 tryptophan 11 to arginine point mutation abolishes DNA binding. 雑誌 Biochim Biophys Acta 1446:140-4 (1999) DOI:10.1016/s0167-4781(99)00078-0 PMID:9765152 (PPP2R1B) 著者 Wang SS, Esplin ED, Li JL, Huang L, Gazdar A, Minna J, Evans GA タイトル Alterations of the PPP2R1B gene in human lung and colon cancer. 雑誌 Science 282:284-7 (1998) DOI:10.1126/science.282.5387.284 |