Chemotherapy Flashcards
Describe some different methods of cancer treatment
Surgery
Chemotherapy - oral and IV
Radiotherapy
Targeted therapies e.g. immunotherapy
Name the different classes of anti-cancer therapeutics COME BACK
Alkylating agents
Antimetabolites
Vinca Alkaloids
Taxanes
Antimitotic Antibiotics
Immunotherapy with monoclonal antibodies
Targeted drugs
Hormonal drugs
Describe the mechanism of action of the alkylating agents class of chemotherapy drugs
Alkylating agents e.g. cisplatin, bisulfan
• Alkyl groups of the drugs allow covalent bonds to form between the drug and DNA
• In this case, it attaches to the guanine between DNA strands at N7 during replication, preventing it from taking place since the strands cannot separate.
What type of drugs are cisplatin, carboplatin and bisulfan?
Alkylating agent
Describe some mechanisms of resistance to alkylating agents
Mechanisms of resistance include:
o Decreased entry or increased removal of a drug by the cell
o Inactivation of the drug by the cell e.g. glutathione
o Enhanced repair of affected DNA by DNA repair enzymes
Describe the mechanism of action of antimetabolite drugs
Similar chemical structure to essential metabolites required by cell prior to cell division.
May be incorporated into new nuclear material or bind irreversibly with vital enzymes to inhibit cell division:
o E.g. antagonise folic acid (methotrexate),
o Antagonise purine (6-mercaptopurine, 6-thioguanine),
o Inhibit thymidylate synthase (5-fluorouracil),
o Incorporate fluoridated nucleoside in place of normal nucleoside (5FU instead of uracil in RNA)
What is methotrexate and what is its mechanism of action?
Antimetabolite, antagonises folic acid synthesis and therefore inhibits purine synthesis
What is 6-mercaptopurine and what is its mechanism of action?
Antimetabolite which inhibits purine synthesis
What is 5-fuorouracil and what is its mechanism of action?
Antimetabolite which inhibits thymidylate synthase and is incorporated into the place of uracil in RNA to prevent transcription
Name two classes of drugs that are derived from plants which act as spindle poisons
Vinca alkaloids
Taxanes
Describe the mechanism of action of vinca alkaloids
Vinca alkaloids - these drugs bind to tubulin and inhibit its polymerisation into microtubules, preventing spindle formation in dividing cells and causing arrest at metaphase. Their effects manifest only during mitosis. They also inhibit other cellular activities that involve the microtubules, such as leukocyte phagocytosis and chemotaxis, as well as axonal transport in neurons. E.g. vincristine
What is vincristine?
Vinca alkaloid
Describe the mechanism of action of taxanes
Taxanes - act on microtubules, stabilising them (in effect ‘freezing’ them) in the polymerised state, achieving a similar effect to that of the vinca alkaloids. E.g. Paclitaxel (IV) and docetaxel (oral)
Give some examples of taxmen drugs
Paclitaxel and Docetaxel
How is paclitaxel administered?
Oral
How is docitaxel administered?
IV
Describe the mechanism of antimitotic antibiotics and give some examples
• Anthracyclines and Non-anthracyclines
o Intercalate and inhibit DNA and RNA synthesis
o Inhibit topoisomerases to prevent transcription and replication
o Membrane binding and increase permeability to various ions
o Generate free radicals to disrupt DNA chain and prevent mitosis
o Metal ion chelation resulting in cytotoxic compounds
o Alkylation blocking DNA replication
• E.g. daunorubicin, doxorubicin
What type of drug is daunorubicin and doxorubicin?
Antimitotic antibiotics
Give some examples of antimitotic antibiotics
Daunorubicin
Doxorubucin
What are the principles that underly combinational chemotherapy treatment?
Combine those with: o Different mechanism of action • Synergistic or at least additive • Reduce risk of developing resistance o Dissimilar toxicity profile e.g. not both with neurotoxicity (cisplatin and taxane)
List some common side effects of chemotherapy treatment
Alopecia Nausea and vomiting Myalgia (muscle pain) Constant fatigue Myelosuppression
Which cytotoxic agents can affect fertility?
Carboplatin
Cisplatin
Which cytotoxic agents can cause cardiotoxicity?
Cisplatin
5-fluorouracil
Which cytotoxic drug can cause pulmonary fibrosis?
Methotrexate
Bisulfan
What is phlebitis and what can cause it?
Inflammation of a vein, usually caused by trauma, inactivity though can be caused by insertion of cannula or recurrent infusions and injections
Give three targets of hormonal drugs given in cancer
o Anti-oestrogen Tamoxifen, aromatase inhibitors for breast cancer
o Gonadorelin analogue e.g. Goseralin (Zoladex) for prostate and breast cancer
o Anti-androgen (CPA, flutamide) for prostate cancer
What is tamoxifen?
Anti-oestrogen, used in breast cancer
What drug is an anti-oestrogen used in breast cancer?
Tamoxifen
What is Goseralin (Zoladex)?
Gonadorelin analogue for breast and prostate cancer
Name a gonadorelin analogue used to treat certain breast and prostate cancers
Goseralin (Zoladex)
What is Flutamide (CPA)?
Anti-androgen used in prostate cancer
Name an anti-androgen drug used in some prostate cancers?
Flutamide (CPA)
Give some examples of targeted drugs
o Epidermal growth factor receptor (EGFR) Gefitinib (Iressa)/Erlotinib for lung cancer and some breast cancer
o Vascular endothelial receptor (VEGF) Bevacizumab (Avastin)
o Multiple targets sorafenib, sunitinib, etc
What drugs target EGFR and are used to treat lung cancer and some breast cancers?
Gefitinib (Iressa) and Erlotinib
Gefitinib (Iressa) and Erlotinib: what are they good for?
Lung cancer and some breast cancer
Name a CTLA-4 inhibitor?
Ipilimumab
What is ipilimumab?
Anti-CTLA4 monoclonal antibody
Nivolumab, Pembrolizumab, Atezolizumab, Durvalumab, and Avelumab are all examples of what?
PD-L1 inhibitors
Name some PD-L1 inhibitors
Nivolumab, Pembrolizumab, Atezolizumab, Durvalumab, and Avelumab
