Module 17 - Part 2

Question 1

Mechanism of action of Mitotic inhibitors.

Answer 1

Act during the cell cycle to inhibit mitosis, and thus cell division.

Question 2

What are the two subclasses of mitotic inhibitors?

Answer 2

Vinca alkaloids

Taxanes

Question 3

Describe the mechanism of action of Vinca alkaloids.

Answer 3

Block mitosis during metaphase

Bind to tubulin, disrupting MT organization –> inappropriate chromosomal distribution and eventual cell death

Question 4

Describe the mechanism of action of Taxanes.

Answer 4

Act late in G2, prior to M phase.

Stabilize MT bundles –> prevent cell division

Question 5

Describe the mechanism of action/use of glucocorticoids.

Answer 5

Toxic to lymphoid tissues and are thus used in lymphoid tissue-derived cancer.
Use as an adjunct to other chemotherapeutic agents.

Question 6

What are the side effects of glucocorticoids?

Answer 6

Osteoporosis, adrenal insufficiency, susceptibility to infection, GI ulceration, electrolyte disturbance, growth retardation

Question 7

What are other uses of glucocorticoids?

Answer 7

Can be helpful in management of complications of other chemotherapy drugs including reduction in nausea and vomiting, reduction of pain, improved appetite.

Question 8

What is the primary goal of prostate cancer treatment?

Answer 8

Prostate tissue (neoplastic or otherwise) is androgen dependent, so the goal in the treatment of prostate cancer is androgen (i.e. testosterone) deprivation

Question 9

What are the ways in which androgens are deprived for prostate cancer treatment?

Answer 9

Gonadotropin releasing hormone (GnRH) agonists or surgical castration
Androgen receptor antagonists

Question 10

Describe the action of GnRH agonists.

Answer 10

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.

Question 11

Describe the action of androgen receptor antagonists.

Answer 11

Used in combination with GnRH agonists or castration.

Act by blocking androgen receptors in tumour cells.

Question 12

Most common cancer affecting women.

Answer 12

Breast cancer

Question 13

What is the primary pharmacological treatment of breast cancer? Why?

Answer 13

Depriving breast cancer cells of estrogen is the primary pharmacological treatment of breast cancer.
This is because estrogen causes breast tumour cells to proliferate

Question 14

Although blocking estrogen is the primary pharmacological treatment of breast cancer, what is important to note in the treatment of breast cancer?

Answer 14

Estrogen receptor antagonism is used as an adjunct to surgery and radiation therapy

Question 15

Pharmacological treatment of breast cancer can be divided into three major classes, what are they?

Answer 15

Anti-estrogens
Aromatase inhibitors
Trastuzumab

Question 16

Describe the most commonly prescribed drug for breast cancer, the drug type and its mechanism of action.

Answer 16

Tamoxifen - anti-estrogen = partial estrogen receptor agonist/antagonist –> minimally activates the receptor, thereby blocking the binding of endogenous estrogen to the estrogen receptor.

Question 17

Process of inhibiting the conversion of androgens into estrogen.

Answer 17

aromatase inhibitors.

Question 18

What is the mechanism of action of aromatase inhibitors?

Answer 18

Inhibit the conversion of androgens to estrogen, and thus decrease free estrogen available to breast cancer cells.

Question 19

Aromatase inhibitors are only useful in a subset of women, why?

Answer 19

Only effective in post-menopausal women as aromatase inhibitors do not inhibit ovarian estrogen synthesis.

Question 20

In a subset of breast cancer, patients have an increased number of ________ receptors.

Answer 20

HER2 - human epidermal growth factor 2

Question 21

Describe HER2 and cancers with it.

Answer 21

Transmembrane receptor that helps regulate cell growth

Cancers with HER2 are especially aggressive in terms of tumour growth

Question 22

What is the primary treatment for breast caners with HER2?

Answer 22

Trastuzumab (monoclonal antibody) - binds to HER2 and prevents cell proliferation

Question 23

How must trastuzumab be administered?

What are the major side effects?

Answer 23

IV - since it is an antibody and can be degraded in gastric acid
Most prominent adverse effect is cardiotoxicity

Question 24

Enzymes that phosphorylate proteins on specific amino acid residues.

Answer 24

Kinases

Question 25

Increased activity of ______ kinases has been observed in many human cancers.

Answer 25

tyrosine

Question 26

What is a tyrosine kinase inhibitor drug to treat cancer?

Answer 26

Imatinib

Question 27

Imatinib:

• effective in treating?
• Mechanism of action?
• Side effects?

Answer 27

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