Cancer 9: Biological basis of cancer therapy

Question 1

What are the main anti-cancer treatment modalities?

Answer 1

Surgery
Radiotherapy
Chemotherapy
Immunotherapy

Question 2

What are the types of genetic mutations causing cancer?

Answer 2

• Chromosome translocation
• Gene amplification (copy number variation)
• Point mutations within promoter or enhancer regions of genes
• Deletions or insertions
• Epigenetic alterations to gene expression
• Can be inherited

See lecture 2 on cancer

Question 3

List compounds used for cytotoxic chemotherapy

Answer 3

1) Alkylating agents
2) Antimetabolites
3) Anthracyclines
4) Topoisomerase inhibitors
^ (targets slide 15)
5) Vinca alkaloids and taxanes
^ (targets slide 15)

Targeted therapies

1) Small molecules inhibitors
2) Monoclonal antibodies

Question 4

How do cytotoxics work?

Answer 4

They “select” rapidly dividing cells by targeting their structures (mostly the DNA)

Question 5

Describe cytotoxic chemotherapy

Answer 5

Given intravenously or by mouth (occasionally)
Works systemically
Non “targeted” – affects all rapidly dividing cells in the body

Given post-operatively: adjuvant

• Pre-operatively: neoadjuvant
• As monotherapy or in combination
• with curative or palliative intent

Question 6

Describe alkylating agents

Answer 6

• Add alkyl (CNH2N+1) groups to guanine residues in DNA
• Cross-link (intra, inter, DNA-protein) DNA strands and prevents DNA from uncoiling at replication
• Trigger apoptosis (via checkpoint pathway)
• Encourage miss-pairing - oncogenic

Question 7

Describe pseudo-alkylating agents

Answer 7

• Add platinum to guanine residues in DNA

- Same mechanism of cell death as akylating agents

Question 8

List some alkylating agents

Answer 8

Chlorambucil, cyclophosphamide, dacarbazine, temozolomide.

Question 9

List some pseudoalkylating agents

Answer 9

carboplatin, cisplatin, oxaliplatin

Question 10

What are some side effects of alkylating and pseudoalkylating agents?

Answer 10

cause hair loss (not carboplatin), nephrotoxicity, neurotoxicity, ototoxicity (platinums), nausea, vomiting, diarrhoea, immunosuppression, tiredness

Question 11

Describe anti-metabolites?

Answer 11

Masquerade as purine or pyrimidine residues leading to inhibition of DNA synthesis, DNA double strand breaks and apoptosis

Block DNA replication (DNA-DNA) and transcription (DNA –RNA)
Can be purine (adenine and guanine), pyrimidine (thymine/uracil and cytosine) or folate antagonists (which inhibit dihydrofolate reductase required to make folic acid, an important building block for all nucleic acids – especially thymine)