43. Anti-Cancer Agents 1 Flashcards
What are the 3 main approaches to eliminating cancer?
Surgery
Radiotherapy
Chemotherapy
What is adjuvant therapy?
Systematic therapy used in patients with primary tumour removed but at risk for metastasis
What is neoadjuvant therapy?
Treatment given prior to local therapy
Shrinks tumour before surgery
What does classical chemotherapy target?
The cell cycle: proliferation
What are the 4 classes of cytotoxic drugs?
Antimetabolites
Alkylating agents
Cytotoxic antibiotics
Plant alkaloids/microtubule inhibitors
How do antimetabolites work?
Act as competitive antagonists to the metabolic pathways in the biosynthesis of DNA and RNA
What is the most widely used folate antagonist drug?
Methotrexate
What are the two types of antimetabolites?
Folate antagonists
Nucleic acid synthesis inhibitors
How does methotrexate work?
Inhibits dihydrofolate reductase (enzyme that converts folates to tetrahydrofolate)
How do nucleic acid synthesis inhibitors work?
Form false RNA/DNA which is unable/slower to replicate
What nucleic acid synthesis inhibitor is widely used for colorectal cancer?
5-Fluorouracil
5-FU
How does 5-FU work?
Inhibits thymidylate synthase
Incorporation of its metabolites into RNA and DNA
What is the name of the oral version of 5-FU?
Capecitabine
How do alkylating agents work?
Form covalent bonds with DNA
Inhibits DNA synthesis in S phase and interferes with transcription
Contains reactive alkyl groups which form covalent bonds with guanine residues
Name 3 types of alkylating agents
Nitrogen mustards (cyclophosphamide)
Nitrosoureas (Carmustine)
Alkylating-like (cisplatin)
How do cytotoxic antibiotics work?
Prevent cell division
Molecules lodge between DNA coils and distort shape, prevents cell replication
Name an anthracycline
Doxorubicin
How does doxorubicin work?
Stops uncoiling of DNA by stopping DNA-topoisomerase 2 from leaving
What is the adverse effect of doxorubicin?
Cardiac toxicity
Produces O2 radicals which are normally broken down by catalase (low conc in heart) and glutathione peroxidase (inhibited by doxorubicin)
What are the two types of plant alkaloids?
Vinca alkaloids
Taxanes
How do vinca alkaloids work?
Spindle poison
Binds to tubulin and inhibits it polymerising into microtubules
Name 2 vinca alkaloids
Vincristine
Vinblastine
Name 2 taxanes
Paclitaxel
Docetaxel
How do taxanes work?
Promotes formation of intracellular microtubules and prevents their dissassembly
What ways can drug resistance manifest?
Decrease in amount taken up Insufficient activation Increased conc of target enzyme Alternative metabolic pathways Repair of drug induced lesion
What is multidrug resistance?
Simultaneous resistance to many structurally dissimilar anticancer drugs
Development of transport proteins to pump drug out of cancer cell
