Module 17 - Part 2 Flashcards
Mechanism of action of Mitotic inhibitors.
Act during the cell cycle to inhibit mitosis, and thus cell division.
What are the two subclasses of mitotic inhibitors?
Vinca alkaloids
Taxanes
Describe the mechanism of action of Vinca alkaloids.
Block mitosis during metaphase
Bind to tubulin, disrupting MT organization –> inappropriate chromosomal distribution and eventual cell death
Describe the mechanism of action of Taxanes.
Act late in G2, prior to M phase.
Stabilize MT bundles –> prevent cell division
Describe the mechanism of action/use of glucocorticoids.
Toxic to lymphoid tissues and are thus used in lymphoid tissue-derived cancer.
Use as an adjunct to other chemotherapeutic agents.
What are the side effects of glucocorticoids?
Osteoporosis, adrenal insufficiency, susceptibility to infection, GI ulceration, electrolyte disturbance, growth retardation
What are other uses of glucocorticoids?
Can be helpful in management of complications of other chemotherapy drugs including reduction in nausea and vomiting, reduction of pain, improved appetite.
What is the primary goal of prostate cancer treatment?
Prostate tissue (neoplastic or otherwise) is androgen dependent, so the goal in the treatment of prostate cancer is androgen (i.e. testosterone) deprivation
What are the ways in which androgens are deprived for prostate cancer treatment?
Gonadotropin releasing hormone (GnRH) agonists or surgical castration
Androgen receptor antagonists
Describe the action of GnRH agonists.
GnRH causes release of test from the testes.
Test feeds prostate cancer cells but acts by negative feedback to inhibit further GnRH release.
The net effect is decreased testosterone synthesis and release.
Describe the action of androgen receptor antagonists.
Used in combination with GnRH agonists or castration.
Act by blocking androgen receptors in tumour cells.
Most common cancer affecting women.
Breast cancer
What is the primary pharmacological treatment of breast cancer? Why?
Depriving breast cancer cells of estrogen is the primary pharmacological treatment of breast cancer.
This is because estrogen causes breast tumour cells to proliferate
Although blocking estrogen is the primary pharmacological treatment of breast cancer, what is important to note in the treatment of breast cancer?
Estrogen receptor antagonism is used as an adjunct to surgery and radiation therapy
Pharmacological treatment of breast cancer can be divided into three major classes, what are they?
Anti-estrogens
Aromatase inhibitors
Trastuzumab
Describe the most commonly prescribed drug for breast cancer, the drug type and its mechanism of action.
Tamoxifen - anti-estrogen = partial estrogen receptor agonist/antagonist –> minimally activates the receptor, thereby blocking the binding of endogenous estrogen to the estrogen receptor.
Process of inhibiting the conversion of androgens into estrogen.
aromatase inhibitors.
What is the mechanism of action of aromatase inhibitors?
Inhibit the conversion of androgens to estrogen, and thus decrease free estrogen available to breast cancer cells.
Aromatase inhibitors are only useful in a subset of women, why?
Only effective in post-menopausal women as aromatase inhibitors do not inhibit ovarian estrogen synthesis.
In a subset of breast cancer, patients have an increased number of ________ receptors.
HER2 - human epidermal growth factor 2
Describe HER2 and cancers with it.
Transmembrane receptor that helps regulate cell growth
Cancers with HER2 are especially aggressive in terms of tumour growth
What is the primary treatment for breast caners with HER2?
Trastuzumab (monoclonal antibody) - binds to HER2 and prevents cell proliferation
How must trastuzumab be administered?
What are the major side effects?
IV - since it is an antibody and can be degraded in gastric acid
Most prominent adverse effect is cardiotoxicity
Enzymes that phosphorylate proteins on specific amino acid residues.
Kinases
Increased activity of ______ kinases has been observed in many human cancers.
tyrosine
What is a tyrosine kinase inhibitor drug to treat cancer?
Imatinib
Imatinib:
- effective in treating?
- Mechanism of action?
- Side effects?
Effective in treating CML (chronic myelogenous leukemia) and GIST (gastrointestinal stromal tumours)
Causes complete inhibition of cellular proliferatoin and induces apoptosis
Sides: nausea, vomiting, edema and muscle cramps
