Lecture 16 Chemotherapy Targeting mitosis, transcription factors and signal transduction Flashcards
Give examples of steroid hormone sensitive cancers and the hormones they are associated with
breast cancer - estrogen
prostate cancer - androgen
What is meant by the term ‘hormone responsive’ cancer
Giving hormone treatment regresses the cancer
What is meant by the term ‘hormone-dependent’ cancer
Removing/inhibiting the hormone regresses the cancer
What is meant when it is said that the hormones require ‘intracellular cytoplasmic receptors’?
Hormone must bind to the intracellular cytoplasmic receptors which are transcriptional factors
When bound, activation of the transcriptional factors occurs and bind to chromatin, upregulating genes for cellular growth
Explain how tamoxifen works
Tamoxifen is structurally similar to estrogen - competitively binds to the estrogen receptors to block the activation of transcription factors and therefore limits cellular growth
Why should tamoxifen only be given for a limited period of time?
acts as a weak estrogen and could possibly stimulate precancerous lesions
Therefore should only be used for up to around 5 years
What is tamoxifen often combined with if given to a pre-menopausal woman?
leuprolide i.e. gonadotropin-releasing hormone, GnRH, analog - all involved in the production of estrogen
in what form is tamoxifen given?
oral
How is tamoxifen excreted?
bile
feces
Explain why aromatase inhibitors are needed and how they work
in postmenopausal woman, peripheral synthesis of estrogen can occur e.g. liver, fat, etc. - caused by the enzyme aromatase
Therefore if inhibitors of aromatase are given this estrogen production can be limited
Name examples of aromatase inhibitors
Anastrozole
Letrozole
In what form are aromatase inhibitors given?
oral
How are aromatase inhibitors metabolized?
liver
Name examples of non-steriodal anti-androgen drugs
Flutamide
Nilutamide
Bicalutamide
How do anti-androgen drugs work and which cancer is it used to treat?
competitively binds with androgens to the androgen receptor
Works for androgen +ve prostatic cancers
Explain the function of the EGF receptor and its link to breast and lung cancer
EGF = epidermal growth factor
It is an intracellular tyrosine kinase domain protein
When activated, tyrosine is phosphorylated and activation of the signal transduction cascade and cell proliferation occurs
Oncogene versions of EGF present in lung or breast cancers - either overexpression or mutated e.g. constitutive active
What are the brand names of specific tyrosine kinase inhibitors
Iressa
Tarceva
Explain what the BCR-ABL protein is
produced due to chromosomal translocation i.e. swapping of different parts of chromosomes
This protein has tyrosine kinase activity, therefore, can activate cell proliferation
In what cancer is the BCR-ABL protein specific for?
chronic myelogenous leukemia
Name the inhibitor of BCR-ABL and its success
Imatinib (Gleevec)
96% of patients result in remission
In what form is Gleevec/Imatinib given?
Oral
How is Gleevec/Imatinib excreted?
fecally
Which tumor suppressor gene is mutated in around 50% of human cancers?
P53
P53 forms a protein complex with what in cancer cells to degrade P53
MDM2 oncogene
Attaches ubiquitin to P53
