2.3 Platinum based cancer drugs

Question 1

Are platinum based drugs Alkylating agents

Answer 1

Yes

Question 2

Give an example of 3 platinum based drugs and comment on toxicity

Answer 2

Cisplatin
- N&V +++ & nephrotoxic

Oliplatin
- N&V plus sensory neuropathy

Ocaliplatin
- More favourable side effect profile

Question 3

What is the suffix for all platinum based drugs?

Answer 3

Platin

Question 4

What is the mode of action of platinum based drugs?

Answer 4

Formation of DNA Crosslinks:

• Platinum drugs enter cancer cells and form covalent bonds with DNA molecules.
• Specifically, they bind to the nitrogen atoms of purine bases (adenine and guanine) in the DNA double helix.

DNA Damage:
* The binding of platinum drugs to DNA leads to the formation of intrastrand and interstrand crosslinks.
* In intrastrand crosslinking, platinum atoms bind to adjacent guanine bases on the same DNA strand, distorting the DNA structure.
* In interstrand crosslinking, platinum atoms bind to guanine bases on opposite DNA strands, causing the strands to become linked together.

DNA Repair Inhibition:
* The presence of platinum-induced DNA crosslinks interferes with the normal functioning of cellular DNA repair mechanisms.
* Cells attempt to repair the DNA damage caused by platinum drugs, but the crosslinks prevent successful repair.

Cell Cycle Arrest and Apoptosis:
* The accumulation of unrepaired DNA damage triggers cell cycle arrest and activates programmed cell death, known as apoptosis.
* Cancer cells with extensive DNA damage induced by platinum drugs undergo apoptosis, leading to their destruction.

Question 5

How does the toxicity profile of each platinum based drug differ?

Answer 5

Cisplatin
- N&V +++ & nephrotoxic

Oliplatin
- N&V plus sensory neuropathy

Ocaliplatin
- More favourable side effect profile