Inhibitors of metabolism in melanoma therapy (Homo sapiens)

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Description

Key metabolic pathways in melanoma, glycolytic pathway, TCA cycle, glutamine metabolism, and oxidative phosphorylation, with potential therapeutic targets and inhibitors. Inhibitors targeting critical metabolic nodes are outlined in teal. This pathway is based on [Figure 1 in Shen et al](https://www.nature.com/articles/s41420-025-02617-3).

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Quality Tags

Ontology Terms

 

Bibliography

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  1. Audrito V, Managò A, La Vecchia S, Zamporlini F, Vitale N, Baroni G, Cignetto S, Serra S, Bologna C, Stingi A, Arruga F, Vaisitti T, Massi D, Mandalà M, Raffaelli N, Deaglio S; ''Nicotinamide Phosphoribosyltransferase (NAMPT) as a Therapeutic Target in BRAF-Mutated Metastatic Melanoma.''; J Natl Cancer Inst, 2018 PubMed Europe PMC Scholia
  2. Haq R, Shoag J, Andreu-Perez P, Yokoyama S, Edelman H, Rowe GC, Frederick DT, Hurley AD, Nellore A, Kung AL, Wargo JA, Song JS, Fisher DE, Arany Z, Widlund HR; ''Oncogenic BRAF regulates oxidative metabolism via PGC1α and MITF.''; Cancer Cell, 2013 PubMed Europe PMC Scholia
  3. Gopal YN, Rizos H, Chen G, Deng W, Frederick DT, Cooper ZA, Scolyer RA, Pupo G, Komurov K, Sehgal V, Zhang J, Patel L, Pereira CG, Broom BM, Mills GB, Ram P, Smith PD, Wargo JA, Long GV, Davies MA; ''Inhibition of mTORC1/2 overcomes resistance to MAPK pathway inhibitors mediated by PGC1α and oxidative phosphorylation in melanoma.''; Cancer Res, 2014 PubMed Europe PMC Scholia
  4. Chang MT, Tsai LC, Nakagawa-Goto K, Lee KH, Shyur LF; ''Phyto-sesquiterpene lactones DET and DETD-35 induce ferroptosis in vemurafenib sensitive and resistant melanoma via GPX4 inhibition and metabolic reprogramming.''; Pharmacol Res, 2022 PubMed Europe PMC Scholia
  5. Zhang G, Frederick DT, Wu L, Wei Z, Krepler C, Srinivasan S, Chae YC, Xu X, Choi H, Dimwamwa E, Ope O, Shannan B, Basu D, Zhang D, Guha M, Xiao M, Randell S, Sproesser K, Xu W, Liu J, Karakousis GC, Schuchter LM, Gangadhar TC, Amaravadi RK, Gu M, Xu C, Ghosh A, Tian T, Zhang J, Zha S, Liu Q, Brafford P, Weeraratna A, Davies MA, Wargo JA, Avadhani NG, Lu Y, Mills GB, Altieri DC, Flaherty KT, Herlyn M; ''Targeting mitochondrial biogenesis to overcome drug resistance to MAPK inhibitors.''; J Clin Invest, 2016 PubMed Europe PMC Scholia
  6. Houles T, Gravel SP, Lavoie G, Shin S, Savall M, Méant A, Grondin B, Gaboury L, Yoon SO, St-Pierre J, Roux PP; ''RSK Regulates PFK-2 Activity to Promote Metabolic Rewiring in Melanoma.''; Cancer Res, 2018 PubMed Europe PMC Scholia
  7. Shin S, Yang S, Kim M, Lee EK, Hur SC, Jeong SM; ''Fatty acid oxidation supports melanoma cell migration through autophagy regulation.''; Biochem Biophys Res Commun, 2023 PubMed Europe PMC Scholia
  8. Aloia A, Müllhaupt D, Chabbert CD, Eberhart T, Flückiger-Mangual S, Vukolic A, Eichhoff O, Irmisch A, Alexander LT, Scibona E, Frederick DT, Miao B, Tian T, Cheng C, Kwong LN, Wei Z, Sullivan RJ, Boland GM, Herlyn M, Flaherty KT, Zamboni N, Dummer R, Zhang G, Levesque MP, Krek W, Kovacs WJ; ''A Fatty Acid Oxidation-dependent Metabolic Shift Regulates the Adaptation of BRAF-mutated Melanoma to MAPK Inhibitors.''; Clin Cancer Res, 2019 PubMed Europe PMC Scholia
  9. Ishak Gabra MB, Yang Y, Li H, Senapati P, Hanse EA, Lowman XH, Tran TQ, Zhang L, Doan LT, Xu X, Schones DE, Fruman DA, Kong M; ''Dietary glutamine supplementation suppresses epigenetically-activated oncogenic pathways to inhibit melanoma tumour growth.''; Nat Commun, 2020 PubMed Europe PMC Scholia
  10. Hlavaty SI, Salcido KN, Pniewski KA, Mukha D, Ma W, Kannan T, Cassel J, Srikanth YVV, Liu Q, Kossenkov A, Salvino JM, Chen Q, Schug ZT; ''ACSS1-dependent acetate utilization rewires mitochondrial metabolism to support AML and melanoma tumor growth and metastasis.''; Cell Rep, 2024 PubMed Europe PMC Scholia
  11. Chen Y, Wang C, Wu Y, Wang Y, Meng Y, Wu F, Zhang H, Cheng YY, Jiang X, Shi J, Li H, Zhao P, Wu J, Zheng B, Jin D, Bu W; ''Nutrient-delivery and metabolism reactivation therapy for melanoma.''; Nat Nanotechnol, 2024 PubMed Europe PMC Scholia
  12. Stine ZE, Schug ZT, Salvino JM, Dang CV; ''Targeting cancer metabolism in the era of precision oncology.''; Nat Rev Drug Discov, 2022 PubMed Europe PMC Scholia
  13. Fontana F, Macchi C, Anselmi M, Rizzuto AS, Ruscica M, Limonta P; ''PGC1-α-driven mitochondrial biogenesis contributes to a cancer stem cell phenotype in melanoma.''; Biochim Biophys Acta Mol Basis Dis, 2024 PubMed Europe PMC Scholia
  14. Zhang D, Li J, Wang F, Hu J, Wang S, Sun Y; ''2-Deoxy-D-glucose targeting of glucose metabolism in cancer cells as a potential therapy.''; Cancer Lett, 2014 PubMed Europe PMC Scholia
  15. Hernandez-Davies JE, Tran TQ, Reid MA, Rosales KR, Lowman XH, Pan M, Moriceau G, Yang Y, Wu J, Lo RS, Kong M; ''Vemurafenib resistance reprograms melanoma cells towards glutamine dependence.''; J Transl Med, 2015 PubMed Europe PMC Scholia
  16. Shen D, Zhang L, Li S, Tang L; ''Metabolic reprogramming in melanoma therapy.''; Cell Death Discov, 2025 PubMed Europe PMC Scholia
  17. Jeong DI, Hao Q, Lee SY, Kim S, Karmakar M, Chu S, Park M, Cho HJ; ''Cellulose nanocrystal-annealed hydrogel system for local chemo-metabolic therapy of melanoma.''; J Control Release, 2025 PubMed Europe PMC Scholia
  18. Li X, Wu J, Zhang X, Chen W; ''Glutathione reductase-mediated thiol oxidative stress suppresses metastasis of murine melanoma cells.''; Free Radic Biol Med, 2018 PubMed Europe PMC Scholia
  19. Rodrigues MF, Obre E, de Melo FH, Santos GC Jr, Galina A, Jasiulionis MG, Rossignol R, Rumjanek FD, Amoêdo ND; ''Enhanced OXPHOS, glutaminolysis and β-oxidation constitute the metastatic phenotype of melanoma cells.''; Biochem J, 2016 PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
142302view09:34, 31 December 2025Egonwmim-translocation
142203view21:49, 15 December 2025EgonwRemoved two old, empty remarks
142200view17:17, 15 December 2025Khanspersremoving extra erroneous description from gpml
142197view17:22, 12 December 2025Khanspersupdated pathway node shape types
142194view05:25, 11 December 2025KhanspersOntology Term : 'altered metabolic pathway' added !
142193view05:24, 11 December 2025Khanspersupdated mTORC1 complex, added xrefs
142192view04:27, 11 December 2025KhanspersOntology Term : 'melanoma pathway' added !
142191view04:26, 11 December 2025KhanspersModified description
142190view04:23, 11 December 2025KhanspersModified description
142189view04:15, 11 December 2025Khanspersadded xrefs for compounds
142188view03:23, 11 December 2025Khanspersadded xrefs for compounds
142187view02:35, 11 December 2025Khanspersadded xrefs for compounds
142171view00:18, 9 December 2025Khanspersadded cell, updated layout
142170view23:58, 8 December 2025Khansperslayout
142169view23:47, 8 December 2025KhanspersAdded details for MAPK arm
142168view23:32, 8 December 2025Khansperswork in progress
142167view21:21, 8 December 2025Khansperswork in progress
142166view20:42, 8 December 2025Khanspersadded literature, updated interactions
142107view01:08, 2 December 2025KhanspersNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
2-AAPAMetabolite11409146 (PubChem-compound)
2-Deoxy-D-glucoseMetaboliteCHEBI:15866 (ChEBI)
ACSS1GeneProductACSS1 (HGNC)
ARAFGeneProduct369 (Entrez Gene)
AZD2014MetaboliteHMDB0248783 (HMDB)
AZD3965 Metabolite1448671-31-5 (CAS)
AZD8055MetaboliteCHEBI:91329 (ChEBI)
AcetateMetabolite30089 (ChEBI)
Acetyl-CoAMetaboliteHMDB0001206 (HMDB)
BPTESMetabolite314045-39-1 (CAS)
BRAFGeneProduct673 (Entrez Gene)
CB-839Metabolite71577426 (PubChem-compound)
CPT1AGeneProduct1374 (Entrez Gene)
Citric acidMetaboliteHMDB0000094 (HMDB)
DCAMetabolite25975 (PubChem-compound)
DETMetabolite6325056 (PubChem-compound)
DETD-35Metabolite129294656 (PubChem-compound)
DLATGeneProductDLAT (HGNC)
DLDGeneProductDLD (HGNC)
Electron transport chain: OXPHOS system in mitochondriaPathwayWP111 (WikiPathways)
EtomoxirMetabolite9840324 (PubChem-compound)
FA-CoAMetabolite83139 (ChEBI)
FK866Metabolite6914657 (PubChem-compound)
Fructose 1,6-bisphosphateMetaboliteHMDB0001058 (HMDB)
Fructose 6PMetaboliteCHEBI:61527 (ChEBI)
FumarateMetaboliteHMDB0000134 (HMDB)
G6PDGeneProduct2539 (Entrez Gene)
GLSGeneProduct2744 (Entrez Gene)
GMKX1778Metabolite200484-11-3 (CAS)
GPX4GeneProduct2879 (Entrez Gene)
GSRGeneProduct2936 (Entrez Gene)
GSSGMetabolite1372 (ChEMBL compound)
GamitrinibMetabolite25232582 (PubChem-compound)
Glucose-6PMetaboliteCHEBI:75052 (ChEBI) Glucose-6-Phosphate (2-)
GlucoseMetaboliteHMDB0000122 (HMDB)
GlutamateMetaboliteCHEBI:14321 (ChEBI)
GlutamineMetabolite18050 (ChEBI)
GlutathioneMetaboliteCHEBI:57925 (ChEBI)
Indole-5,6-quinoneMetabolite27406 (ChEBI)
Isocitric acidMetaboliteHMDB0000193 (HMDB)
L-DONMetabolite9087 (PubChem-compound)
L-DOPAMetabolite15765 (ChEBI)
L-OHMetabolite
L-OOHMetabolite
L-TyrosineMetabolite17895 (ChEBI)
LDHAGeneProduct3939 (Entrez Gene)
LDHBGeneProduct3945 (Entrez Gene)
LactateMetaboliteHMDB0000190 (HMDB)
MAP2K1GeneProduct5604 (Entrez Gene)
MAP2K2GeneProduct5605 (Entrez Gene)
MAPK1GeneProduct5594 (Entrez Gene)
MAPK3GeneProduct5595 (Entrez Gene)
MITFGeneProduct4286 (Entrez Gene)
MLST8GeneProductMLST8 (HGNC)
MTORGeneProductMTOR (HGNC)
MTyr-OANPsMetabolite
MalateMetaboliteHMDB0000744 (HMDB)
NADMetaboliteHMDB00902 (HMDB)
NADPMetaboliteCHEBI:18009 (ChEBI)
NADPHMetaboliteHMDB00221 (HMDB)
NAMMetaboliteCHEBI:17154 (ChEBI)
NAMPTGeneProduct10135 (Entrez Gene)
NMNMetabolite16171 (ChEBI)
OPiMetabolite86711931 (PubChem-compound)
OxaloacetateMetaboliteHMDB0000223 (HMDB)
P-enolpyruvateMetaboliteHMDB0000263 (HMDB)
PDHA1GeneProductPDHA1 (HGNC)
PDKGeneProduct2.7.11.2 (Enzyme Nomenclature)
PFKFB2GeneProductPFKFB2 (HGNC)
PGLSGeneProduct25796 (Entrez Gene)
PKLRGeneProduct5313 (Entrez Gene)
PKM1GeneProduct5315 (Entrez Gene)
PKM2GeneProduct5315 (Entrez Gene)
PPARGC1AGeneProduct10891 (Entrez Gene)
PhenforminMetaboliteHMDB15050 (HMDB)
PyruvateMetaboliteHMDB0000243 (HMDB)
RAF1GeneProduct5894 (Entrez Gene)
RPS6KA1GeneProduct6195 (Entrez Gene)
RPS6KA2GeneProduct6196 (Entrez Gene)
RPS6KA3GeneProduct6197 (Entrez Gene)
RPTORGeneProductRPTOR (HGNC)
SLC16A1GeneProductSLC16A1 (HGNC)
SLC16A3GeneProductSLC16A3 (HGNC)
SLC1A5GeneProductSLC1A5 (HGNC)
SLC2A1GeneProduct6513 (Entrez Gene)
SR-18292Metabolite129896798 (PubChem-compound)
SuccinateMetaboliteHMDB0000254 (HMDB)
TCA cyclePathwayWP78 (WikiPathways)
TRAP1GeneProductTRAP1 (HGNC) Mitochondrial Hsp90
XCT790MetaboliteQ8041720 (Wikidata)
alpha-Ketoglutaric acidMetaboliteHMDB0000208 (HMDB)
succinyl-CoAMetaboliteHMDB0001022 (HMDB)

Annotated Interactions

No annotated interactions

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