Final Review

Question 1

Cancer
- What do E6 and E7 HPV oncogenes do?
- Synthetic lethality
- 3 cytotoxic agents

Answer 1

• Inhibit retinoblastoma protein (tumor suppressor) and degrade p53, blocking apoptosis
• Mutation of either of 2 genes is not lethal. Mutation of both is lethal
• Methotrexate, 5-fluorouracil, Cytarabine

Question 2

Cancer
- Which drug is given after giving MTX? why?
- 5-FU mechanism
- Effect
- 3 FOLFOX components
- 2 Cancer resistance to 5-FU?
- Cytarabine analog of which molecule?
- Mechanism (2)
- How does it stop DNA elongation?
- 2 alkylating agents

Answer 2

• Leucovorin to let normal cells recover if they’re affected by MTX
• Inhibits thymidylate synthase by competing with dUMP
• dUTP increase + dNTP imbalance = DNA damage
• Leucovorin, 5-FU, and oxaliplatin
• High levels of pyrophophatase dUTPase and dTMP salvaged by thymidine through thymidine kinase (TK)
• dC
• DNA chain terminator and competitive inhibitor of DNA polymerase
• Unnatural conformation
• Cyclophosphamide and platins

Question 3

Cancer
- Active metabolite of cyclophosphamide
- Advantage of cyclophosphamide
- Platins activation
- Platins mechanism
- Name of antitumor antibiotic
- mechanism and effect
- Etoposide mechanism
- Topotecan and SN-38 mechanism
- What is Irinotecan activated by? Why does it exist?
- What does TOP1 do?
- What do taxanes and vincas target?
- Name of 1 taxane
- How does it target microtubules?
- Why does Abraxane exist?
- What is Abraxene composed of?

Answer 3

• Phosphamide mustard
• Little drug interactions because it needs so many CYP450s to be activated
• Water molecules replace leaving groups
• platinum-DNA adduct prevents unwinding and causes DNA damage
• Doxorubicin
• Stabilize TOP2-DNA reaction intermediate, preventing protein-linked DNA to rejoin
• Same as Doxorubicin
• SN-38 = active form of Irinotecan. Stabilize TOP1-DNA complex
• Esterase
• Sn-38 has bad solubility
• Makes nicks that provides swivel points for DNA to rotate, uncoil, and relax it for replication and transcription
• Microtubules
• Paclitaxel
• Stabilize them
• It helps paclitaxel solubilize and also reduces toxicity and does not cause hypersensitivity reactions unlike solvent-based and surfactant-based formulations
• Albumin that surrounds paclitaxel