Flashcards in Anti cancer drugs Deck (53):
Target unique structure (or expressed element) or process associated with cancerous cell
What is the mechanism of alkylating agents?
Insert alkyl group into DNA structure; cross-link between adjacent bases, particularly guanine bases, as well as proteins; cause stress in molecules leading to strand breaks and apoptosis
Which stage of the cell cycle do alkylating agents target?
generally, cycle non-specific
What does a bifunctional alkylating agent do?
Causes intrastrand linking and cross-linking
Why are cytotoxic antibiotics used in cancer therapy?
Too toxic to use in infectious disease therapy; the cost vs benefit ratio is different in cancer
What is the mechanism of cytotoxic antibiotics?
Inhibit transcription and translation processes
What do antimetabolites do?
Substitute themselves in the DNA synthesis pathway, block DNA synthesis, make molecule non-functional
Which stage of the cell cycle to antimetabolites target?
What are the three pathways by which antimetabolites may block DNA synthesis?
Folate pathway, pyrimidine base synthesis, purine base synthesis
Which pathway does methotrexate target?
Folate pathway, similar shape to folic acid
What is the mechanism of mitotic poisons?
Inhibit microtubule function so that mitotic spindles don't form or inhibit topoisomerase
Which stage of the cell cycle to mitotic poisons target?
Examples of mitotic poisons?
vinca alkaloids (from periwinkle plant), taxanes (European yew tree), etiposide (mandrake)
What is the mechanism of SERM?
Selective oestrogen receptor modulator agonises some oestrogen receptors (for bone development and blood coagulation) and antagonises others (in breast tissue)
What is the mechanism of aromatase inhibitors?
Lower circulating oestrogen (aromatase is used by fat cells to convert precursor substances into oestrogen)
2 drug groups used to treat breast cancer?
SERM and aromatase inhibitors
2 drug groups used to treat prostate cancer?
antiandrogens and gonadotrophin-RH analogues
Mechanism of antiandrogens?
Prevent access to growth factor, stops growth of cancer
Mechanism of gonadotrophin-RH analogues
Gonadotrophin releasing hormone, released from hypothalamus to act on pituitary gland to stimulate LH and FSH; analogue is given repeatedly to change HP axis and cause a decrease in LH secretion
Drug group used to treat blood-borne cancers e.g. leukaemia, lymphoma
Mechanism of action of glucocorticoids
High doses lead to lysis of affected cells
Common adverse effects of glucocorticoids
Also target rapidly dividing normal cell populations:
alopecia (hair follicles)
skin blistering and necrosis
gastrointestinal sores (stomatitis) and mouth inflammation (mucositis)
nausea and vomiting
infertility (for duration of therapy)
bone marrow suppression (bone marrow cells have rapid turnover)
organ toxicity - may occur after therapy is finished
Examples of organ toxicity from glucocorticoids
heart: dysrhythmia and altered contractility, acute heart failure
Kidneys: renal failure
nervous system: paraesthesias (numbness, tingling, burning sensation as a result of altered axonal transport) microtubules affecting cell division and axonal transport
urinary bladder: haemorrhagic cystitis
What are 2 drug groups that address the adverse drug reactions (ADR) of glucocorticoids?
Colony stimulating factors
Examples of antiemetic drugs
- dopamine/serotonin/neurokinin receptor antagonists e.g. dopamine connecting medulla to vomiting centre
- metoclopramide (maxolon) = dopamine receptor antagonist, ondansetron = serotonin receptor antagonist, aprepitant (Emend) = substance P receptor antagonist
- glucocorticoids (dexamethasone)
Examples of CSFs
Colony stimulating factors
Mechanism for CSFs
stimulate white blood cell populations
What compound can be used to manage organ toxicity?
Mesna for alkylating agents (cyclophosphamide and ifosfamide)
Mechanism of Mesna?
Prevents formation of metabolite that causes hemorrhagic cystitis without affecting the metabolite that's causing the desired action
Describe monoclonal antibody production
Mouse immunised, antibody-forming cells taken out of spleen, tumour cells are grown in tissue culture, antibody-forming cells are fused with the tumour cells, antibody-producing 'hybridomas' are cloned
Drug group rutiximab belongs to and mechanism of action?
Monoclonal antibody. Targets CD20 surface antigen over expressed on B cells in non-Hodgkin's lymphoma, triggering B cell lysis.
Drug group trastuzumab (Herceptin) belongs to and mechanism of action
Monoclonal antibody. Binds to human epidermal growth factor 2, which is over expressed in some forms of breast cancer
What might be attached to monoclonal antibodies?
Examples of biological response markers?
Interferons and interleukin-2
Mechanism of interferons
augment the cytotoxicity of immune cells (NK and T cells, macrophages); high doses inhibit cell proliferation and facilitate cytotoxicity, alter antigen expression on tumour cells and immune cells
Mechanism of interleukin-2
Stimulates lymphocyte proliferation and cellular immunity
remove patient's lymphocytes, grow in culture
sensitise against tumour antigens by giving them IL-2
more aggressive immune response against tumour
What cytokine can be used as a novel agent in the treatment of sampled immune cells?
Mechanism of protein kinase inhibitors
small molecule drugs bind to enzyme's ATP binding site, inactivating the enzyme
Examples of protein kinases targeted
tyrosine kinase, serine-threonine kinase
What types of cancers do you use protein kinase inhibitors?
leukaemia, GIT tumours
*common suffix -inib
What else might protein kinases inhibit?
What's an example of a sensitising agent? What disease does it protect against? Describe the mechanism
BCG used to immunise against tuberculosis.
Involves mycobacterium bovis preparation.
BCG instilled into urinary bladder tumour.
Makes cells more reactive
Induces inflammatory reaction
Superficial cancer cells are more likely to be attacked by the immune cells.
What might complicate treatment?
Drug resistance, tumour cell sanctuaries and dose exhaustion
How does drug resistance arise?
Through spontaneous mutations that afford cancer cells protection against drug
What are strategies that address drug resistance?
Multiple cytotoxic drug therapy
Number of drugs with differing actions
What are tumour cell sanctuaries?
Cells grow in compartments that are relatively inaccessible to the drugs, creating sites of relapse
What are strategies to address tumour cell sanctuaries?
radiotherapy or surgery
What events occur in dose exhaustion?
Maximum therapeutic doses and patient immune response is not sufficient to attack remaining cells
Why can't the dose be increased in dose exhaustion?
Dose exhaustion occurs at the maximum therapeutic response and the patient immune response is not sufficient to attack remaining cells. Can't push doses into the toxic range.
What are strategies to address dose exhaustion?
Multiple drug therapy, Radiotherapy, chemotherapy combinations
What type of anticancer drug is methotrexate?
As an anti-inflammatory drug, what is methotrexate used for?
DMARD (disease-modifying antirheumatic drug) used to treat rheumatic arthritis