1. Cancer Metabolism & Cancer Genetics
Presented by Sungmin Lee
Biochemistry Lab.

2. Asp-Arg- succinate Cycle
Overview of metabolism
Acyl CoA
Glyoxylate Cycle
Lipid
Electron Transport Chain
TCA Cycle
NADH, FADH2
Glycolysis
Glucose
Asp-Arg- succinate Cycle
Carbon skeleton R
ATP
Urea Cycle
Amino group
Amino acid

3. Altered cancer metabolism
Glycolysis
Amino acid cycle
β-oxidation
doi: /nrc

4. Cancer glycolysis - Warburg effect
Increased glucose uptake
Increased glycolysis
Decreased use of pyruvate to TCA cycle
Increased lactate production
Increased angiogenesis .
Warburg effect

5. Cancer glycolysis - GLUT
Cancers 2013, 5(4),
Clin Cancer Res Nov 1;19(21):

6. Cancer glycolysis - GLUT
Oncogenic mutation & hypoxic condition resulted in up-regulation of glycolytic enzymes.
FEBS Lett Jul 31;581(19):

7. Cancer glycolysis - PHGDH
Metabolite flux 3PG to serine biosynthesis increased availability of glutamine/α-KG to TCA cycle.
It shows that suppression of TCA cycle does not always contribute to cancer progression.
Nature Aug 18;476(7360):

8. Relapse Free Survival Probability
Cancer glycolysis - PHGDH
Relapse Free Survival Probability
Time (months)
Cell May 9;153(4):
Cancer Res Aug 1;76(15):
The importance of the PHGDH as a therapeutic target is suggested by current studies.

9. Cancer glycolysis - PKM2
Clin Cancer Res Oct 15;18(20):
Nature, 2014, 508(10):

10. Cancer glycolysis - PKM2
Clin Cancer Res Oct 15;18(20):
Cancer Lett Jan 28;356(2 Pt A):184-91

11. Cancer amino acid cycle - ASS1
Decreased expression of ASS1 resulted in deficiency of arginine (= Arginine auxotrophy)
Int. J. Cancer, 2009, 125:

12. Cancer amino acid cycle - ASS1
Int J Cancer Jun 15;126(12):
PLoS One Mar 16;11(3):e
Arginine auxotrophy can induce not only alteration of metabolic intermediates but induce chemoresistance including platinum resistance which firstly reported ASS1-related resistance.

13. Cancer amino acid cycle - GLO1
Oncogene (2015) 34:1196–1206
Exp. Cell Res. 2012, 318:

14. Cancer fat metabolism - FASN
Nat Rev Cancer Oct;7(10):

15. Cancer fat metabolism - FASN
Evid Based Complement Alternat Med. 2014;2014:232946
Nat Rev Cancer Oct;7(10):

16. Cancer fat metabolism - IDHs
R132H
Clin Cancer Res, (20):
Acta Neuropathol :597–602

17. Cancer fat metabolism - IDHs
D-2HG can induce epigenetic alteration in cancer including methylation and histone modification to morph cells to cancer stem cell-like phenotypes.
According to the reason above, D-2HG is called by “oncometabolite”

18. Cancer therapies Metformin : activates of AMPK and reduce glycolysis
CBR-5884 : PHDGH inhibitor
α-Methyl-DL-aspartic acid
: ASS1 specific inhibitor
NCT-502 : currently suggested PHDGH inhibitor
TVB-3166 : FASN specific inhibitor
Nat Chem Biol Jun;12(6):452-8
PLoS One Dec 11;10(12):e

19. Thank you for your attention !