44. Anti-Cancer Agents 2 Flashcards
What are the limitations of classic chemotherapy?
Target proliferation, not invasion or metastasis Lack of selectivity Lack of sensitivity (high doses) Don't totally eliminate tumour Resistance
What is tamoxifen?
Selective estrogen receptor modulator
Antagonist of estrogen receptor in breast
How does tamoxifen work?
Converted to active metabolite
Binds to estrogen receptor
Binding of drug and receptor to oestrogen-response element inhibits transcription of oestrogen-responsive genes
Dissociates slowly and interferes with receptor recycling
What are the adverse effects of tamoxifen?
Hot flushes Irregular menstrual cucles Vaginal discharge Increased risk endometrial cancer DVT and PE
How is oestrogen made in premenopausal women?
Testosterone converted to estradiol in ovary (aromatisation)
How is oestrogen made in postmenopausal women?
Androstenedione converted to estrone in adipose tissue (peripheral aromatisation)
How do aromatase inhibitors work?
Inhibition of peripheral aromatisation
What does HER2 do?
Plays a role in transmission of signals that ensure controlled cell growth and regulated rate of division
What does overexpression of HER2 cause?
Sustained activation
Growth promoting signals are permanently transmitted to nucleus
How is HER2 detected?
Immunohistochemical analysis of protein (HercepTest)
FISH detects gene
How does Trastuzumab/Herceptin work?
Monoclonal antibody directed against HER2
Blocks receptors dimerising
Flags tumour cell for destruction by immune system
What is the Philadelphia chromosome?
Shortened chromosome 22 due to translocation between chromosomes 9 and 22
Produces BCR-ABL oncogene
Present in 95% of chronic myeloid leukaemia
What drug targets the BCR/ABL oncogene?
Imatinib
Selective tyrosine kinase inhibitor
Name a drug that inhibits small molecule receptor tyrosine kinases
Sunitinib
Name a drug that is a neutralising antibody to growth factors
anti-VEGF: Bevacizumab
Avastin
