Non-small cell lung cancer (WP4255)

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.
last edited

Authors

Khanspers, AlexanderPico, Egonw, Fehrhart, and Finterly

Cited In

Organism

Homo sapiens

Communities

CPTAC Diseases

Annotations

Pathway Ontology: lung cancer pathway disease pathway cancer pathway

Cell Type Ontology: bronchial epithelial cell

Disease Ontology: lung cancer

Participants

Label Type Compact Identifier
EGF GeneProduct ensembl:ENSG00000138798
PIK3CA GeneProduct ensembl:ENSG00000121879
CRABP1 GeneProduct ensembl:ENSG00000166426
EML4 GeneProduct ensembl:ENSG00000143924
PIK3R1 GeneProduct ensembl:ENSG00000145675
DAG Metabolite chebi:18035
BAK1 GeneProduct ensembl:ENSG00000030110
TGFA GeneProduct ensembl:ENSG00000163235
AKT1 GeneProduct ensembl:ENSG00000142208
PIP3 Metabolite chebi:16618
HRAS GeneProduct ensembl:ENSG00000174775
KRAS GeneProduct ensembl:ENSG00000133703
CDKN1A GeneProduct ensembl:ENSG00000124762
BAD GeneProduct ensembl:ENSG00000002330
PDK1 GeneProduct ensembl:ENSG00000152256
omacetaxine mepesuccinate Metabolite chebi:71019
RB1 GeneProduct ensembl:ENSG00000139687
binimetinib Metabolite wikidata:Q19903515
Ca2+ Metabolite chebi:22984
CDKN2A GeneProduct ensembl:ENSG00000147889
RASSF1 GeneProduct ensembl:ENSG00000068028
EGFR GeneProduct ensembl:ENSG00000146648
JAK3 GeneProduct ensembl:ENSG00000105639
trametinib Metabolite wikidata:Q7833138
Retinoic acid Metabolite chebi:6067
pimasertib Metabolite wikidata:Q27088393
IP3 Metabolite chebi:16595
PRKCA GeneProduct ensembl:ENSG00000154229
STK4 GeneProduct ensembl:ENSG00000101109
selumetinib Metabolite chebi:90227
Calcium Signaling Pathway Pathway None
RARB GeneProduct ensembl:ENSG00000077092
cobimetinib Metabolite wikidata:Q15708292
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
KRAS GeneProduct ensembl:ENSG00000133703
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
PI3K-Akt Signaling Pathway Pathway wikipathways:WP4172
ALK GeneProduct ensembl:ENSG00000171094
STAT3 GeneProduct ensembl:ENSG00000168610
STAT5A GeneProduct ensembl:ENSG00000126561
STAT5B GeneProduct ensembl:ENSG00000173757
PIK3CA GeneProduct ensembl:ENSG00000121879
PIK3CB GeneProduct ensembl:ENSG00000051382
PIK3CD GeneProduct ensembl:ENSG00000171608
PIK3R2 GeneProduct ensembl:ENSG00000105647
PIK3R3 GeneProduct ensembl:ENSG00000117461
Ras Signaling Pathway Pathway wikipathways:WP4223
CCND1 GeneProduct ensembl:ENSG00000110092
RASSF5 GeneProduct ensembl:ENSG00000266094
RXRA GeneProduct ensembl:ENSG00000186350
RXRB GeneProduct ensembl:ENSG00000204231
RXRG GeneProduct ensembl:ENSG00000143171
CDK6 GeneProduct ensembl:ENSG00000105810
CCND1 GeneProduct ensembl:ENSG00000110092
E2F1 GeneProduct ensembl:ENSG00000101412
E2F2 GeneProduct ensembl:ENSG00000007968
E2F3 GeneProduct ensembl:ENSG00000112242
p53 Signaling Pathway Pathway wikipathways:WP707
Cell Cycle Pathway wikipathways:WP179
Cell Cycle Pathway wikipathways:WP179
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
CASP9 GeneProduct ensembl:ENSG00000132906
CYCS GeneProduct ensembl:ENSG00000172115
Retinoic acid Metabolite chebi:6067
CRABP2 GeneProduct ensembl:ENSG00000143320

References

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  4. AACR Project GENIE Consortium. AACR Project GENIE: Powering Precision Medicine through an International Consortium. Cancer Discov. 2017 Aug;7(8):818–31. PubMed Europe PMC Scholia