Entry |
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Name |
Small cell lung cancer - Homo sapiens (human)
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Description |
Lung cancer is a leading cause of cancer death among men and women in industrialized countries. Small cell lung carcinoma (SCLC) is a highly aggressive neoplasm, which accounts for approximately 25% of all lung cancer cases. Molecular mechanisms altered in SCLC include induced expression of oncogene, MYC, and loss of tumorsuppressor genes, such as p53, PTEN, RB, and FHIT. The overexpression of MYC proteins in SCLC is largely a result of gene amplification. Such overexpression leads to more rapid proliferation and loss of terminal differentiation. Mutation or deletion of p53 or PTEN can lead to more rapid proliferation and reduced apoptosis. The retinoblastoma gene RB1 encodes a nuclear phosphoprotein that helps to regulate cell-cycle progression. The fragile histidine triad gene FHIT encodes the enzyme diadenosine triphosphate hydrolase, which is thought to have an indirect role in proapoptosis and cell-cycle control.
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Class |
Human Diseases; Cancer: specific types
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Pathway map |

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Network |
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Element |
N00051 | Deleted PTEN to PI3K signaling pathway |
N00052 | Mutation-inactivated PTEN to PI3K signaling pathway |
N00074 | Loss of RB1 to cell cycle G1/S |
N00075 | Mutation-inactivated RB1 to cell cycle G1/S |
N00088 | Amplified MYC to p15-cell cycle G1/S |
N00089 | Amplified MYC to cell cycle G1/S |
N00092 | Amplified MYC to p27-cell cycle G1/S |
N00100 | BCL2-overexpression to intrinsic apoptotic pathway |
N00115 | Mutation-inactivated TP53 to transcription |
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Disease |
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Drug |
D11987 | Trilaciclib dihydrochloride |
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Organism |
Homo sapiens (human) [GN: hsa]
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Gene |
5915 | RARB; retinoic acid receptor beta [KO:K08528] |
1026 | CDKN1A; cyclin dependent kinase inhibitor 1A [KO:K06625] |
1647 | GADD45A; growth arrest and DNA damage inducible alpha [KO:K04402] |
4616 | GADD45B; growth arrest and DNA damage inducible beta [KO:K04402] |
10912 | GADD45G; growth arrest and DNA damage inducible gamma [KO:K04402] |
581 | BAX; BCL2 associated X, apoptosis regulator [KO:K02159] |
578 | BAK1; BCL2 antagonist/killer 1 [KO:K14021] |
1643 | DDB2; damage specific DNA binding protein 2 [KO:K10140] |
596 | BCL2; BCL2 apoptosis regulator [KO:K02161] |
317 | APAF1; apoptotic peptidase activating factor 1 [KO:K02084] |
4609 | MYC; MYC proto-oncogene, bHLH transcription factor [KO:K04377] |
7709 | ZBTB17; zinc finger and BTB domain containing 17 [KO:K10500] |
1030 | CDKN2B; cyclin dependent kinase inhibitor 2B [KO:K04685] |
1163 | CKS1B; CDC28 protein kinase regulatory subunit 1B [KO:K02219] |
1164 | CKS2; CDC28 protein kinase regulatory subunit 2 [KO:K02219] |
6502 | SKP2; S-phase kinase associated protein 2 [KO:K03875] |
1027 | CDKN1B; cyclin dependent kinase inhibitor 1B [KO:K06624] |
5925 | RB1; RB transcriptional corepressor 1 [KO:K06618] |
1284 | COL4A2; collagen type IV alpha 2 chain [KO:K06237] |
1286 | COL4A4; collagen type IV alpha 4 chain [KO:K06237] |
1288 | COL4A6; collagen type IV alpha 6 chain [KO:K06237] |
1282 | COL4A1; collagen type IV alpha 1 chain [KO:K06237] |
1287 | COL4A5; collagen type IV alpha 5 chain [KO:K06237] |
1285 | COL4A3; collagen type IV alpha 3 chain [KO:K06237] |
3674 | ITGA2B; integrin subunit alpha 2b [KO:K06476] |
5290 | PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153] |
5293 | PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153] |
5291 | PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153] |
5295 | PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649] |
5296 | PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649] |
8503 | PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649] |
1147 | CHUK; component of inhibitor of nuclear factor kappa B kinase complex [KO:K04467] [EC:2.7.11.10] |
8517 | IKBKG; inhibitor of nuclear factor kappa B kinase regulatory subunit gamma [KO:K07210] |
4790 | NFKB1; nuclear factor kappa B subunit 1 [KO:K02580] |
5970 | RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735] |
329 | BIRC2; baculoviral IAP repeat containing 2 [KO:K16060] |
330 | BIRC3; baculoviral IAP repeat containing 3 [KO:K16060] |
79444 | BIRC7; baculoviral IAP repeat containing 7 [KO:K16061] |
7185 | TRAF1; TNF receptor associated factor 1 [KO:K03172] |
7187 | TRAF3; TNF receptor associated factor 3 [KO:K03174] |
9618 | TRAF4; TNF receptor associated factor 4 [KO:K09848] |
7188 | TRAF5; TNF receptor associated factor 5 [KO:K09849] |
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Compound |
C05981 | Phosphatidylinositol-3,4,5-trisphosphate |
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Reference |
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Authors |
Osada H, Takahashi T. |
Title |
Genetic alterations of multiple tumor suppressors and oncogenes in the carcinogenesis and progression of lung cancer. |
Journal |
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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 |
Kaye FJ. |
Title |
Molecular biology 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 |
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Authors |
Altucci L, Gronemeyer H. |
Title |
The promise of retinoids to fight against cancer. |
Journal |
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Reference |
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Authors |
Virmani AK, Rathi A, Zochbauer-Muller S, Sacchi N, Fukuyama Y, Bryant D, Maitra A, Heda S, Fong KM, Thunnissen F, Minna JD, Gazdar AF. |
Title |
Promoter methylation and silencing of the retinoic acid receptor-beta gene in lung carcinomas. |
Journal |
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Reference |
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Authors |
Sartorius UA, Krammer PH. |
Title |
Upregulation of Bcl-2 is involved in the mediation of chemotherapy resistance in human small cell lung cancer cell lines. |
Journal |
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Reference |
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Authors |
Adhikary S, Eilers M. |
Title |
Transcriptional regulation and transformation by Myc proteins. |
Journal |
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Reference |
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Authors |
Spruck C, Strohmaier H, Watson M, Smith AP, Ryan A, Krek TW, Reed SI. |
Title |
A CDK-independent function of mammalian Cks1: targeting of SCF(Skp2) to the CDK inhibitor p27Kip1. |
Journal |
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Reference |
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Authors |
Buttery RC, Rintoul RC, Sethi T. |
Title |
Small cell lung cancer: the importance of the extracellular matrix. |
Journal |
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Reference |
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Authors |
Yamada KM, Araki M. |
Title |
Tumor suppressor PTEN: modulator of cell signaling, growth, migration and apoptosis. |
Journal |
J Cell Sci 114:2375-82 (2001) |
Reference |
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Authors |
Rintoul RC, Sethi T. |
Title |
The role of extracellular matrix in small-cell lung cancer. |
Journal |
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Reference |
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Authors |
Ekedahl J, Joseph B, Grigoriev MY, Muller M, Magnusson C, Lewensohn R, Zhivotovsky B. |
Title |
Expression of inhibitor of apoptosis proteins in small- and non-small-cell lung carcinoma cells. |
Journal |
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Reference |
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Authors |
Shivapurkar N, Reddy J, Chaudhary PM, Gazdar AF. |
Title |
Apoptosis and lung cancer: a review. |
Journal |
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Reference |
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Authors |
Weyhenmeyer B, Murphy AC, Prehn JH, Murphy BM |
Title |
Targeting the anti-apoptotic Bcl-2 family members for the treatment of cancer. |
Journal |
Exp Oncol 34:192-9 (2012) |
Related pathway |
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KO pathway |
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LinkDB |
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