cancer part 3

Question 1

What are plants’ Alkaloids?

Answer 1

High molecular weight, highly lipophilic natural products

Question 2

State the two types of plant Alkaloids

Answer 2

Microtubule inhibitors
Topoisomerase inhibitors

Question 3

State how plant alkaloids act as an anti-cancer agent

Answer 3

Disrupt balance between polymerised and depolymerised microtubules
Cell cycle specific

Question 4

list the two classes of drugs that are microtubule inhibitors

Answer 4

Vinca alkaloids and Taxanes

Question 5

Vinca alkaloids are derived from?

Answer 5

periwinkle plant

Question 6

List examples of drugs that are vinca alkaloids

Answer 6

Vincristine, vinblastine, vinorelbine

Question 7

what is Vinblastine indicated for?

Answer 7

metastatic testicular carcinoma and lymphomas
VB is administered with bleomycin/cisplatin

Question 8

What is the Vincristine indicated?

Answer 8

Childhood ALL- Acute lymphoblastic leukaemia; Wilm’s tumour, lymphomas

Question 9

What is Vinorelbine indicated for

Answer 9

Advanced non-small cell lung cancer

Question 10

What is the mechanism of Vinca alkaloids?

Answer 10

Cell cycle dependent - mitosis is blocked in metaphase
GTP-dependent binding to tubulin - blocks polymerisation - stops microtubule formation
Dysfunctional spindle apparatus - frozen in metaphase - chromosomal segregation stopped

Question 11

State the side effects of Vinca Alkaloids

Answer 11

N/V/D - esp Vincristine
Alopecia
Extravasation
VB - myelosupression
VC - peripheral neuropathy

Question 12

List the examples of Taxanes

Answer 12

Paclitaxel
Docetaxel

Question 13

What is taxol?

Answer 13

derivative of precursors found in yew tree - first member of taxane family studied

Question 14

State the uses of Taxanes

Answer 14

Advanced ovarian and metastatic breast
Also used in
Small cell lung cancer
Many combinations

Question 15

State how mitosis is blocked by paclitaxel?

Answer 15

Usually, stable tubulin molecules stack and fail to depolymerise, cell remains frozen in metaphase

Question 16

State the mechanism of action of Taxanes

Answer 16

Paclitaxel binds tubulin reversibly
Unlike vinca alkaloids it promotes polymerization/ stabilization of tubulin
Shifts equilibrium - formation of microtubules
Overly stable tubules - dysfunctional, cell stopped in metaphase
Cell death

Question 17

Facts about Eribulin

Answer 17

synthetic analogue of potent antitubulin agent halichondrin B.
Halichondrin B is a natural product from a rare Japanese sponge.
third line treatment for cancer
Orally administered

Question 18

State the side effects of Eribulin

Answer 18

low incidence of peripheral neuropathy.
Neutropenia
Fatigue

Question 19

State the difference between vinca Alkaloids and Taxanes?

Answer 19

Taxane inhibit depolymerization while vinca Alkaloids inhibits polymerization

Question 20

State the name of orally available microtubule inhibitor currently in trials for advanced prostate and breast cancer?

Answer 20

Sabizabulin

Question 21

State what topoisomerase 1 inhibitor does?

Answer 21

Topoisomerase 1 induce transient break in single strand and prevent resealing

Question 22

State the role of topoisomerase II inhibitor?

Answer 22

It induces transient break in DNA double strand and prevent resealing

Question 23

State the Mechanism of action of topoisomerase inhibitors

Answer 23

inhibits the cycle (break and resealing) of TOPO at the DNA break point.
It inhibits DNA closing or resealing reaction by forming stable cleavable-TOPO-DNA complex.
It forms indirect protein-associated single and double strand break.

Question 24

List examples of drugs that are topoisomerase 1 inhibitors

Answer 24

Topotecan
Irinotecan

Question 25

List examples of drugs that are topoisomerase II inhibitors

Answer 25

Etoposide, anthracyclines(doxorubicin)