Non-small cell lung cancer (Homo sapiens)

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1, 53ERLegendProliferationApoptosisDNA DamageActivating mutationRetinoic acidEGFEGFRCDKN1ACRABP1AKT1PIP3PDK1EML4IP3PRKCABADKRASCDK4RASSF1Ca2+STK4BAK1DAGPIK3R1CDKN2ATP53PIK3CARB1TGFARARBCalcium Signaling PathwayJAK3HRASPERBB2PPPGRB2SOS1SOS2KRASNRASARAFBRAFRAF1MAP2K1PPMAP2K2PPMAPK1MAPK3PPPPPLCG1PPPLCG2PRKCBPRKCGPIK3CBPIK3CDAKT2AKT3PCASP9PFOXO3PPPI3K-Akt Signaling PathwayALK6STAT3STAT5APSTAT5BPCell survivalPIK3CAPIK3CBPIK3CDPIK3R2PIK3R3Ras Signaling PathwayCCND1RASSF5ApoptosisRXRARXRBRXRGCDK6CCND1E2F1E2F2E2F3G1 to S progressionp53 Signaling PathwayCell CycleCell CycleBAXDDB2GADD45AGADD45BGADD45GPOLKInactivating mutationCASP82FHITBID4ApoptosisCASP3CASP9CYCSRetinoic acidCRABP2Interrupted effectCell cycle arrestCell growth control


Description

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.


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Ontology Terms

 

Bibliography

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  1. Sasaki T, Rodig SJ, Chirieac LR, Jänne PA; ''The biology and treatment of EML4-ALK non-small cell lung cancer.''; Eur J Cancer, 2010 PubMed Europe PMC Scholia
  2. 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; ''Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer.''; Nature, 2007 PubMed Europe PMC Scholia
  3. ''AACR Project GENIE: Powering Precision Medicine through an International Consortium.''; Cancer Discov, 2017 PubMed Europe PMC Scholia
  4. Odogwu L, Mathieu L, Blumenthal G, Larkins E, Goldberg KB, Griffin N, Bijwaard K, Lee EY, Philip R, Jiang X, Rodriguez L, McKee AE, Keegan P, Pazdur R; ''FDA Approval Summary: Dabrafenib and Trametinib for the Treatment of Metastatic Non-Small Cell Lung Cancers Harboring BRAF V600E Mutations.''; Oncologist, 2018 PubMed Europe PMC Scholia
  5. Gainor JF, Curigliano G, Kim DW, Lee DH, Besse B, Baik CS, Doebele RC, Cassier PA, Lopes G, Tan DSW, Garralda E, Paz-Ares LG, Cho BC, Gadgeel SM, Thomas M, Liu SV, Taylor MH, Mansfield AS, Zhu VW, Clifford C, Zhang H, Palmer M, Green J, Turner CD, Subbiah V; ''Pralsetinib for RET fusion-positive non-small-cell lung cancer (ARROW): a multi-cohort, open-label, phase 1/2 study.''; Lancet Oncol, 2021 PubMed Europe PMC Scholia
  6. Deng WG, Nishizaki M, Fang B, Roth JA, Ji L; ''Induction of apoptosis by tumor suppressor FHIT via death receptor signaling pathway in human lung cancer cells.''; Biochem Biophys Res Commun, 2007 PubMed Europe PMC Scholia
  7. Casaluce F, Sgambato A, Maione P, Sacco PC, Santabarbara G, Gridelli C; ''Selumetinib for the treatment of non-small cell lung cancer.''; Expert Opin Investig Drugs, 2017 PubMed Europe PMC Scholia
  8. Donninger H, Vos MD, Clark GJ; ''The RASSF1A tumor suppressor.''; J Cell Sci, 2007 PubMed Europe PMC Scholia
  9. Xu J, Tian L, Qi W, Lv Q, Wang T; ''Advancements in NSCLC: From Pathophysiological Insights to Targeted Treatments.''; Am J Clin Oncol, 2024 PubMed Europe PMC Scholia
  10. Shivakumar L, Minna J, Sakamaki T, Pestell R, White MA; ''The RASSF1A tumor suppressor blocks cell cycle progression and inhibits cyclin D1 accumulation.''; Mol Cell Biol, 2002 PubMed Europe PMC Scholia
  11. Hornbeck PV, Zhang B, Murray B, Kornhauser JM, Latham V, Skrzypek E; ''PhosphoSitePlus, 2014: mutations, PTMs and recalibrations.''; Nucleic Acids Res, 2015 PubMed Europe PMC Scholia
  12. ''KEGG Non-small cell lung cancer''; https://www.kegg.jp/dbget-bin/www_bget?pathway+map05223,
  13. Gautschi O, Park K, Solomon BJ, Tomasini P, Loong HH, De Braud F, Goto K, Peterson P, Barker S, Liming K, Oxnard GR, Frimodt-Moller B, Drilon A; ''Selpercatinib in RET Fusion-Positive Non-Small Cell Lung Cancer: Final Safety and Efficacy, Including Overall Survival, From the LIBRETTO-001 Phase I/II Trial.''; J Clin Oncol, 2025 PubMed Europe PMC Scholia
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  17. Riely GJ, Smit EF, Ahn MJ, Felip E, Ramalingam SS, Tsao A, Johnson M, Gelsomino F, Esper R, Nadal E, Offin M, Provencio M, Clarke J, Hussein M, Otterson GA, Dagogo-Jack I, Goldman JW, Morgensztern D, Alcasid A, Usari T, Wissel P, Wilner K, Pathan N, Tonkovyd S, Johnson BE; ''A plain language summary of the PHAROS study: the combination of encorafenib and binimetinib for people with BRAF V600E-mutant metastatic non-small-cell lung cancer.''; Future Oncol, 2024 PubMed Europe PMC Scholia
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History

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CompareRevisionActionTimeUserComment
142399view19:48, 4 February 2026Khansperswork in progress
142398view19:33, 4 February 2026Khansperswork in progress
142397view19:20, 4 February 2026Khansperswork in progress
142396view19:03, 4 February 2026Khansperswork in progress
142394view22:40, 3 February 2026Khansperslayout, references
142393view23:52, 2 February 2026Khanspersadded literature references, drugs
140411view20:47, 18 August 2025Khanspersupdated ptm
140137view19:02, 31 July 2025Khanspersupdated ptms
140096view01:09, 26 July 2025Khanspersnode size update
140095view01:06, 26 July 2025Khanspersupdated some interactions (to labels) to graphical lines
140033view19:13, 19 July 2025EgonwModified description
140031view19:11, 19 July 2025EgonwCalcium ion with unicode
138079view22:42, 13 March 2025EweitzRefine state position
138069view12:43, 13 March 2025EweitzOntology Term : 'lung large cell carcinoma' added !
138068view12:42, 13 March 2025EweitzOntology Term : 'lung adenocarcinoma' added !
138067view12:42, 13 March 2025EweitzOntology Term : 'squamous cell carcinoma' added !
138066view12:41, 13 March 2025EweitzModified description
138064view12:29, 13 March 2025EweitzOntology Term : 'lung non-small cell carcinoma' added !
138060view12:23, 13 March 2025EweitzMitigate PathVisio / Kaavio graphical discrepancy
138059view12:20, 13 March 2025EweitzFix PathVisio / Kaavio graphical discrepancy
138058view12:20, 13 March 2025EweitzStandardize case
138057view12:18, 13 March 2025EweitzRefine state position
138056view12:10, 13 March 2025EweitzEconomize layout
138055view12:07, 13 March 2025EweitzStandardize case
138054view12:05, 13 March 2025EweitzEconomize layout
138053view12:02, 13 March 2025EweitzEconomize layout
138052view11:54, 13 March 2025EweitzEconomize layout
138051view11:47, 13 March 2025EweitzEconomize layout
138049view11:45, 13 March 2025EweitzStack nodes
138048view11:40, 13 March 2025EweitzTailor node height
137089view22:06, 27 February 2025KhanspersModified description
127755view18:51, 2 December 2023EgonwChEBI id for Ca2+ instead of the "Ca" atom
127573view17:25, 23 October 2023KhanspersModified description
127490view17:13, 11 October 2023Khanspersupdated phosphosites
127237view20:18, 25 August 2023Khanspersadded lit ref and updated description
123348view10:42, 17 July 2022EgonwMade five pathways clickable
119279view10:42, 23 June 2021Finterlyadded KEGG pathway info to publicationXref
108128view10:28, 29 November 2019FehrhartOntology Term : 'lung cancer' added !
108127view10:28, 29 November 2019FehrhartOntology Term : 'cancer pathway' added !
105677view22:54, 12 August 2019Khanspersadded drugs
105676view22:28, 12 August 2019Khanspersupdated outcomes
105481view05:38, 8 August 2019KhanspersModified description
105444view04:55, 8 August 2019KhanspersModified description
105192view23:10, 17 July 2019KhanspersModified description
105191view23:09, 17 July 2019Khanspersupdated lit refs
105190view22:42, 17 July 2019Khanspersupdated ERBB2
105189view22:33, 17 July 2019Khanspersadded lit ref
105155view23:21, 12 July 2019Khanspersadded details for retinoic acid signaling and added new interaction type
105154view22:21, 12 July 2019Khanspersupdate FHIT section
105004view04:55, 28 June 2019KhanspersModified description

External references

DataNodes

View all...
NameTypeDatabase referenceComment
AKT1GeneProductENSG00000142208 (Ensembl)
AKT2GeneProductENSG00000105221 (Ensembl)
AKT3GeneProductENSG00000117020 (Ensembl)
ALKGeneProductENSG00000171094 (Ensembl)
ARAFGeneProductENSG00000078061 (Ensembl)
BADGeneProductENSG00000002330 (Ensembl)
BAK1GeneProductENSG00000030110 (Ensembl)
BAXGeneProductENSG00000087088 (Ensembl)
BIDGeneProductENSG00000015475 (Ensembl)
BRAFGeneProductENSG00000157764 (Ensembl)
CASP3GeneProductENSG00000164305 (Ensembl)
CASP8GeneProductENSG00000064012 (Ensembl)
CASP9GeneProductENSG00000132906 (Ensembl)
CCND1GeneProductENSG00000110092 (Ensembl)
CDK4GeneProductENSG00000135446 (Ensembl)
CDK6GeneProductENSG00000105810 (Ensembl)
CDKN1AGeneProductENSG00000124762 (Ensembl)
CDKN2AGeneProductENSG00000147889 (Ensembl)
CRABP1GeneProductENSG00000166426 (Ensembl)
CRABP2GeneProductENSG00000143320 (Ensembl)
CYCSGeneProductENSG00000172115 (Ensembl)
Ca2+MetaboliteCHEBI:22984 (ChEBI)
Calcium Signaling PathwayPathway
Cell CyclePathwayWP179 (WikiPathways)
DAGMetaboliteCHEBI:18035 (ChEBI)
DDB2GeneProductENSG00000134574 (Ensembl)
E2F1GeneProductENSG00000101412 (Ensembl)
E2F2GeneProductENSG00000007968 (Ensembl)
E2F3GeneProductENSG00000112242 (Ensembl)
EGFGeneProductENSG00000138798 (Ensembl)
EGFRGeneProductENSG00000146648 (Ensembl)
EML4GeneProductENSG00000143924 (Ensembl)
ERBB2GeneProductENSG00000141736 (Ensembl)
FHITGeneProductENSG00000189283 (Ensembl)
FOXO3GeneProductENSG00000118689 (Ensembl)
GADD45AGeneProductENSG00000116717 (Ensembl)
GADD45BGeneProductENSG00000099860 (Ensembl)
GADD45GGeneProductENSG00000130222 (Ensembl)
GRB2GeneProductGRB2 (HGNC)
HRASGeneProductENSG00000174775 (Ensembl)
IP3MetaboliteCHEBI:16595 (ChEBI)
JAK3GeneProductENSG00000105639 (Ensembl)
KRASGeneProductENSG00000133703 (Ensembl)
MAP2K1GeneProductENSG00000169032 (Ensembl)
MAP2K2GeneProductENSG00000126934 (Ensembl)
MAPK1GeneProductENSG00000100030 (Ensembl)
MAPK3GeneProductENSG00000102882 (Ensembl)
NRASGeneProductENSG00000213281 (Ensembl)
PDK1GeneProductENSG00000152256 (Ensembl)
PI3K-Akt Signaling PathwayPathwayWP4172 (WikiPathways)
PIK3CAGeneProductENSG00000121879 (Ensembl)
PIK3CBGeneProductENSG00000051382 (Ensembl)
PIK3CDGeneProductENSG00000171608 (Ensembl)
PIK3R1GeneProductENSG00000145675 (Ensembl)
PIK3R2GeneProductENSG00000105647 (Ensembl)
PIK3R3GeneProductENSG00000117461 (Ensembl)
PIP3MetaboliteCHEBI:16618 (ChEBI)
PLCG1GeneProductENSG00000124181 (Ensembl)
PLCG2GeneProductENSG00000197943 (Ensembl)
POLKGeneProductENSG00000122008 (Ensembl)
PRKCAGeneProductENSG00000154229 (Ensembl)
PRKCBGeneProductENSG00000166501 (Ensembl)
PRKCGGeneProductENSG00000126583 (Ensembl)
RAF1GeneProductENSG00000132155 (Ensembl)
RARBGeneProductENSG00000077092 (Ensembl)
RASSF1GeneProductENSG00000068028 (Ensembl)
RASSF5GeneProductENSG00000266094 (Ensembl)
RB1GeneProductENSG00000139687 (Ensembl)
RXRAGeneProductENSG00000186350 (Ensembl)
RXRBGeneProductENSG00000204231 (Ensembl)
RXRGGeneProductENSG00000143171 (Ensembl)
Ras Signaling PathwayPathwayWP4223 (WikiPathways)
Retinoic acidMetaboliteCHEBI:6067 (ChEBI)
SOS1GeneProductENSG00000115904 (Ensembl)
SOS2GeneProductENSG00000100485 (Ensembl)
STAT3GeneProductENSG00000168610 (Ensembl)
STAT5AGeneProductENSG00000126561 (Ensembl)
STAT5BGeneProductENSG00000173757 (Ensembl)
STK4GeneProductENSG00000101109 (Ensembl)
TGFAGeneProductENSG00000163235 (Ensembl)
TP53GeneProductENSG00000141510 (Ensembl)
p53 Signaling PathwayPathwayWP707 (WikiPathways)

Annotated Interactions

No annotated interactions

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