Biochemistry. 20/02/20
Anti-cancer treatments
1. Learning Outcomes
Outline the principles of cancer development
Integrate knowledge of cellular signalling involved in both cancer development and cell death to
specific drug mechanisms
Describe treatment strategies, relating it to the principles of cancer development
Explain how treatment strategies can be tailored when there are distinctive features which
disseminate normal from cancerous cells.
2. How does cancer occur?
Cancer is a genetic condition. P53 (tumour suppressor gene) stops
cells growing and it’s often mutated in cancers. High energy like sun
rays can damage DNA and can cause a mutation in P53. Can also be
inherited or break in chromosomes while replication that causes a
part of a chromosome to move to another part and we get more
copies of the gene that we would expect to.
Encapsulated:
- Single location, low risk
- Easily treatable, surgically removed and prophylactic
(preventive) chemotherapy.
- May be classified as benign doesn’t mean harmless it
means it’s in one location.
Invasive:
- Aggressive
- Cells move outside a tumour “capsule”
- Metastasis through body
Many cancers are diagnosed late therefore there is high
chance of metastasis.
3. What is the difference between a cancer cell and a non-cancer cell?
They don’t rely on survival signals,
They’re not contact inhibited
May have multiple nuclei
High rate of metabolism
Survive better at low pH and work better in hypoxic environment
Avoid checkpoints in cell cycle
Cancerous cells are cells out of control
4. Cell cycle: Mitotic cell division
Most of our cells are in
phase G0 or ‘G not’, their
metabolising but not
replicating. E.g.
cardiomyocytes. If they
need to replicate they go
into G1. Checkpoint in G1,
P53 important in this
phase
5. Chemotherapy
, Biochemistry. 20/02/20
Anti-cancer treatments
Originally described as: “Drugs that are selectively toxic to invading microorganisms while having
minimal effects on the host”
Now considered to include the treatment of tumours; usually “cytotoxic anti-cancer therapy”
Where in the cell cycle?
CD95 binds to its receptor and recruits an adaptor
protein which recruits a pro-caspase (long
molecules that get cleaved and activated) these
can cleave another caspase and so on causing the
caspases to move into the nucleus and start
degrading nuclear content .P53 can be activated
and act like TF to transcribe CD95 that will go out
and bind again to receptors in cell surface. We
can also get BAX transcription (protein that
localises to the mitochondrial membrane,
punches a hole and lets out cytochrome C which
is part of electron transport chain
Intrinsic pathway is the same process, but
different caspases involved. (there shouldn’t
be two nuclei in the picture, but she did it that
way because if not it wouldn’t fit). DNA
damage occurs and P53 gets phosphorylated
and activated and acts as a TF to make Bax,
Bad and Bid which cause a puncher in the
outer membrane of mitochondria, after this
Cytochrome C (black dots) move outside and
associate with pro-caspase 9, which means we
get caspase dependent DNases being activated
6. DNA synthesis inhibitors:
Anti-cancer treatments
1. Learning Outcomes
Outline the principles of cancer development
Integrate knowledge of cellular signalling involved in both cancer development and cell death to
specific drug mechanisms
Describe treatment strategies, relating it to the principles of cancer development
Explain how treatment strategies can be tailored when there are distinctive features which
disseminate normal from cancerous cells.
2. How does cancer occur?
Cancer is a genetic condition. P53 (tumour suppressor gene) stops
cells growing and it’s often mutated in cancers. High energy like sun
rays can damage DNA and can cause a mutation in P53. Can also be
inherited or break in chromosomes while replication that causes a
part of a chromosome to move to another part and we get more
copies of the gene that we would expect to.
Encapsulated:
- Single location, low risk
- Easily treatable, surgically removed and prophylactic
(preventive) chemotherapy.
- May be classified as benign doesn’t mean harmless it
means it’s in one location.
Invasive:
- Aggressive
- Cells move outside a tumour “capsule”
- Metastasis through body
Many cancers are diagnosed late therefore there is high
chance of metastasis.
3. What is the difference between a cancer cell and a non-cancer cell?
They don’t rely on survival signals,
They’re not contact inhibited
May have multiple nuclei
High rate of metabolism
Survive better at low pH and work better in hypoxic environment
Avoid checkpoints in cell cycle
Cancerous cells are cells out of control
4. Cell cycle: Mitotic cell division
Most of our cells are in
phase G0 or ‘G not’, their
metabolising but not
replicating. E.g.
cardiomyocytes. If they
need to replicate they go
into G1. Checkpoint in G1,
P53 important in this
phase
5. Chemotherapy
, Biochemistry. 20/02/20
Anti-cancer treatments
Originally described as: “Drugs that are selectively toxic to invading microorganisms while having
minimal effects on the host”
Now considered to include the treatment of tumours; usually “cytotoxic anti-cancer therapy”
Where in the cell cycle?
CD95 binds to its receptor and recruits an adaptor
protein which recruits a pro-caspase (long
molecules that get cleaved and activated) these
can cleave another caspase and so on causing the
caspases to move into the nucleus and start
degrading nuclear content .P53 can be activated
and act like TF to transcribe CD95 that will go out
and bind again to receptors in cell surface. We
can also get BAX transcription (protein that
localises to the mitochondrial membrane,
punches a hole and lets out cytochrome C which
is part of electron transport chain
Intrinsic pathway is the same process, but
different caspases involved. (there shouldn’t
be two nuclei in the picture, but she did it that
way because if not it wouldn’t fit). DNA
damage occurs and P53 gets phosphorylated
and activated and acts as a TF to make Bax,
Bad and Bid which cause a puncher in the
outer membrane of mitochondria, after this
Cytochrome C (black dots) move outside and
associate with pro-caspase 9, which means we
get caspase dependent DNases being activated
6. DNA synthesis inhibitors:
