Non-small cell lung cancer (WP4255)

Homo sapiens

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Non-small cell lung cancer (NSCLC) represents 85% of lung cancer and is defined as any type of epithelial lung cancer that is NOT small cell carcinoma, including squamous cell (SCC), adeno (AC) and large-cell carcinoma. Mutations in NSCLC: * KRAS (mutated in ~29% of NSCLC patients) inactivates its GTPase activity and the p21-RAS protein continuously transmits growth signals to the nucleus. * Mutations or overexpression of EGFR (~22% of NSCLC patients) leads to increased proliferation. * The abnormal fusion of EML4-ALK (~5% of NSCLC patients) leads to constitutive ALK activation, which causes cell proliferation, invasion, and inhibition of apoptosis. * Inactivating mutation of p53 (~50% of NSCLC patients) leads to reduced apoptosis and proliferation. * The protein encoded by the p16INK4a, CDKN2A, inhibits formation of CDK-cyclin-D complexes by competitive binding of CDK4 and CDK6. p16INK4a is mutated in ~12% of NSCLC patients, which leads to a loss of this inhibitory effect. * RARB is a nuclear retinoic acid receptor whose function is often lost in NSCLC, leading to a loss of cell growth control. This pathway was developed based on https://www.kegg.jp/dbget-bin/www_bget?pathway+map05223. Phosphorylation sites were added based on information from PhosphoSitePlus (R), www.phosphosite.org.

Authors

Kristina Hanspers , Alex Pico , Egon Willighagen , Friederike Ehrhart , and Finterly Hu

Activity

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Organisms

Homo sapiens

Communities

CPTAC Diseases

Annotations

Pathway Ontology

lung cancer pathway disease pathway cancer pathway

Disease Ontology

lung cancer

Cell Type Ontology

bronchial epithelial cell

Participants
Query Drugst.One

Label Type Compact URI Comment
DAG Metabolite chebi:18035
PIP3 Metabolite chebi:16618
omacetaxine mepesuccinate Metabolite chebi:71019
binimetinib Metabolite wikidata:Q19903515
Ca2+ Metabolite chebi:29108
trametinib Metabolite wikidata:Q7833138
Retinoic acid Metabolite chebi:6067
pimasertib Metabolite wikidata:Q27088393
IP3 Metabolite chebi:16595
selumetinib Metabolite chebi:90227
cobimetinib Metabolite wikidata:Q15708292
EGF GeneProduct ensembl:ENSG00000138798
PIK3CA GeneProduct ensembl:ENSG00000121879
CRABP1 GeneProduct ensembl:ENSG00000166426
EML4 GeneProduct ensembl:ENSG00000143924
PIK3R1 GeneProduct ensembl:ENSG00000145675
BAK1 GeneProduct ensembl:ENSG00000030110
TGFA GeneProduct ensembl:ENSG00000163235
AKT1 GeneProduct ensembl:ENSG00000142208
HRAS GeneProduct ensembl:ENSG00000174775
KRAS GeneProduct ensembl:ENSG00000133703
CDKN1A GeneProduct ensembl:ENSG00000124762
BAD GeneProduct ensembl:ENSG00000002330
PDK1 GeneProduct ensembl:ENSG00000152256
RB1 GeneProduct ensembl:ENSG00000139687
CDKN2A GeneProduct ensembl:ENSG00000147889
RASSF1 GeneProduct ensembl:ENSG00000068028
EGFR GeneProduct ensembl:ENSG00000146648
JAK3 GeneProduct ensembl:ENSG00000105639
PRKCA GeneProduct ensembl:ENSG00000154229
STK4 GeneProduct ensembl:ENSG00000101109
RARB GeneProduct ensembl:ENSG00000077092
CDK4 GeneProduct ensembl:ENSG00000135446
TP53 GeneProduct ensembl:ENSG00000141510
ERBB2 GeneProduct ensembl:ENSG00000141736
GRB2 GeneProduct hgnc.symbol:GRB2
SOS1 GeneProduct ensembl:ENSG00000115904
SOS2 GeneProduct ensembl:ENSG00000100485
NRAS GeneProduct ensembl:ENSG00000213281
ARAF GeneProduct ensembl:ENSG00000078061
BRAF GeneProduct ensembl:ENSG00000157764
RAF1 GeneProduct ensembl:ENSG00000132155
MAP2K1 GeneProduct ensembl:ENSG00000169032
MAP2K2 GeneProduct ensembl:ENSG00000126934
MAPK1 GeneProduct ensembl:ENSG00000100030
MAPK3 GeneProduct ensembl:ENSG00000102882
PLCG1 GeneProduct ensembl:ENSG00000124181
PLCG2 GeneProduct ensembl:ENSG00000197943
PRKCB GeneProduct ensembl:ENSG00000166501
PRKCG GeneProduct ensembl:ENSG00000126583
PIK3CB GeneProduct ensembl:ENSG00000051382
PIK3CD GeneProduct ensembl:ENSG00000171608
AKT2 GeneProduct ensembl:ENSG00000105221
AKT3 GeneProduct ensembl:ENSG00000117020
CASP9 GeneProduct ensembl:ENSG00000132906
FOXO3 GeneProduct ensembl:ENSG00000118689
ALK GeneProduct ensembl:ENSG00000171094
STAT3 GeneProduct ensembl:ENSG00000168610
STAT5A GeneProduct ensembl:ENSG00000126561
STAT5B GeneProduct ensembl:ENSG00000173757
PIK3R2 GeneProduct ensembl:ENSG00000105647
PIK3R3 GeneProduct ensembl:ENSG00000117461
CCND1 GeneProduct ensembl:ENSG00000110092
RASSF5 GeneProduct ensembl:ENSG00000266094
RXRA GeneProduct ensembl:ENSG00000186350
RXRB GeneProduct ensembl:ENSG00000204231
RXRG GeneProduct ensembl:ENSG00000143171
CDK6 GeneProduct ensembl:ENSG00000105810
E2F1 GeneProduct ensembl:ENSG00000101412
E2F2 GeneProduct ensembl:ENSG00000007968
E2F3 GeneProduct ensembl:ENSG00000112242
BAX GeneProduct ensembl:ENSG00000087088
DDB2 GeneProduct ensembl:ENSG00000134574
GADD45A GeneProduct ensembl:ENSG00000116717
GADD45B GeneProduct ensembl:ENSG00000099860
GADD45G GeneProduct ensembl:ENSG00000130222
POLK GeneProduct ensembl:ENSG00000122008
CASP8 GeneProduct ensembl:ENSG00000064012
FHIT GeneProduct ensembl:ENSG00000189283
BID GeneProduct ensembl:ENSG00000015475
CASP3 GeneProduct ensembl:ENSG00000164305
CYCS GeneProduct ensembl:ENSG00000172115
CRABP2 GeneProduct ensembl:ENSG00000143320

References

  1. KEGG Pathway: map05223
  2. Induction of apoptosis by tumor suppressor FHIT via death receptor signaling pathway in human lung cancer cells. Deng WG, Nishizaki M, Fang B, Roth JA, Ji L. Biochem Biophys Res Commun. 2007 Apr 20;355(4):993–9. PubMed Europe PMC Scholia
  3. The biology and treatment of EML4-ALK non-small cell lung cancer. Sasaki T, Rodig SJ, Chirieac LR, Jänne PA. Eur J Cancer. 2010 Jul;46(10):1773–80. PubMed Europe PMC Scholia
  4. Molecular pathways: current role and future directions of the retinoic acid pathway in cancer prevention and treatment. Connolly RM, Nguyen NK, Sukumar S. Clin Cancer Res. 2013 Apr 1;19(7):1651–9. PubMed Europe PMC Scholia
  5. PhosphoSitePlus, 2014: mutations, PTMs and recalibrations. Hornbeck PV, Zhang B, Murray B, Kornhauser JM, Latham V, Skrzypek E. Nucleic Acids Res. 2015 Jan;43(Database issue):D512-20. PubMed Europe PMC Scholia
  6. AACR Project GENIE: Powering Precision Medicine through an International Consortium. AACR Project GENIE Consortium. Cancer Discov. 2017 Aug;7(8):818–31. PubMed Europe PMC Scholia