Cancer metabolism
The metabolism of cancer cells has to change due to their altered physiology compared with that of
the tissue they are derived from – this is a hallmark of cancer. It allows them to be self sufficient and
sustain angiogenesis. A further change in metabolism can result in metastasis. Metabolsim differs by
several ways:
- Increased proliferation
- Mutations in signalling pathways
- De-toxification of anti-cancer therapies (transporters, target alteration, DDR etc.
- Survival in an inhospitable environment (inhibition of apoptosis)
Warburg effect
Describes the high lactate production in the presence of oxygen – also known as aerobic glycolysis.
Producing energy from pyruvate instead of entering the TCA cycle is 100x quicker. It produces an
acidic microenvironment which can be used for diagnosis with a PET scan and a glucose mimetic.
This sort of pet scan is called an FDG PET scan as it uses a fluorescent glucose mimetic which gets
taken up by the cell, phosphorylated and then trapped.
The question is, why do cells use high rates of glycolysis in normoxic conditions?
There are several theories:
- Mitochondrial energy generation has become damaged – Some cancers exhibit mutations
in mitochondrial enzymes such SDH and FH in pheochromocytoma and leiomyoma
respectively.
- Changes in enzyme expression due to different signalling – c-Myc, p53, HIF1, PTEN
- Changes in the requirements for macromolecule synthesis:
Glycolysis is used to produce many more things for the
cancer cell that aren’t in as high demand in normal cells.
Protein is very important in cancer cells. Without this
mechanism the AAs in muscles begin to become
catabolised to keep up with the demands of tumour and
result in muscle wastage. This is a similar reason as to
why most people with cancers die of organ starvation,
thus a therapy against conversion of muscle into tumour
mass may prolong the patient’s life.
The metabolism of cancer cells has to change due to their altered physiology compared with that of
the tissue they are derived from – this is a hallmark of cancer. It allows them to be self sufficient and
sustain angiogenesis. A further change in metabolism can result in metastasis. Metabolsim differs by
several ways:
- Increased proliferation
- Mutations in signalling pathways
- De-toxification of anti-cancer therapies (transporters, target alteration, DDR etc.
- Survival in an inhospitable environment (inhibition of apoptosis)
Warburg effect
Describes the high lactate production in the presence of oxygen – also known as aerobic glycolysis.
Producing energy from pyruvate instead of entering the TCA cycle is 100x quicker. It produces an
acidic microenvironment which can be used for diagnosis with a PET scan and a glucose mimetic.
This sort of pet scan is called an FDG PET scan as it uses a fluorescent glucose mimetic which gets
taken up by the cell, phosphorylated and then trapped.
The question is, why do cells use high rates of glycolysis in normoxic conditions?
There are several theories:
- Mitochondrial energy generation has become damaged – Some cancers exhibit mutations
in mitochondrial enzymes such SDH and FH in pheochromocytoma and leiomyoma
respectively.
- Changes in enzyme expression due to different signalling – c-Myc, p53, HIF1, PTEN
- Changes in the requirements for macromolecule synthesis:
Glycolysis is used to produce many more things for the
cancer cell that aren’t in as high demand in normal cells.
Protein is very important in cancer cells. Without this
mechanism the AAs in muscles begin to become
catabolised to keep up with the demands of tumour and
result in muscle wastage. This is a similar reason as to
why most people with cancers die of organ starvation,
thus a therapy against conversion of muscle into tumour
mass may prolong the patient’s life.
