2.7 Mitotic inhibitors

Question 1

What are the 5 different classes of chemotherapy?

Answer 1

• Alkylating agents
• Antimetabolites
• Topoisomerase inhbitors
• Mitotic inhibitors
• Anti tumour antibiotics

Question 2

What other description are mitotic inhibitors often given?

Answer 2

Tubulin inhibitors

Often used interchangeably with mitotic inhibitors

Question 3

Which phase of the cell cycle do Mitotic inhibitors influence

Mitotic inhibitors often used interchangeably with tubulin inhibitors

Answer 3

M Phase.

Question 4

What is the mode of action of mitotic inhibitors?

Mitotic inhibitors often used interchangeably with tubulin inhibitors

Answer 4

• Microtubules are a critical component of the mitotic spindle that separate chromosomes during cell division.
• Mitotic inhibitors Inhibit or arrest cell division (Mitosis) by disrupting microtubule function
• They do this in the M phase of the cell cycle.

Question 5

What are 3 types of mitotic inhibitors

Mitotic inhibitors often used interchangeably with tubulin inhibitors

Answer 5

• Vinca Alkaloids
• Taxanes
• Epothiolones

Question 6

Name 3 types of Vinca Alkaloids?

Vinca Alcaloids/Taxanes/Epothiolones

Answer 6

• Vinblastine
• Vincristine
• Vinorelbine

Question 7

What is the specific mode of action of Vinca Alkaloids?

Vinca Alcaloids/Taxanes/Epothiolones

Answer 7

• They bind to tubulin, which is a constituent protein of microtubules
• Interrupting polymerisation and formation resulting in mitotic arrest, which stops cell division

Question 8

What is the main issue with Vinca Alkaloids?

Answer 8

Vinca Alkaloids are associated with neurotoxicity and can influence the peripheral, autonomic and central nervous system

Question 9

Name 4 types of Taxanes?

Answer 9

• Paclitaxel
• Nab-paclitaxel
• Docetaxel
• Calzitaxel

Question 10

What typical suffix for taxanes?

Answer 10

Taxel

Question 11

What is the mode of action of Taxanes?

Answer 11

**Stabilization of Microtubules:
**
* Taxanes bind to a specific site on the microtubules within the cell.
* By doing so, they stabilize the microtubules, preventing them from depolymerizing or breaking down.
* This stabilization effect interferes with the normal dynamics of microtubules during cell division.

Mitotic Arrest:
* By stabilizing microtubules, taxanes disrupt the normal process of mitosis, or cell division.
* They prevent the mitotic spindle (a structure made of microtubules) from properly forming and functioning.
* As a result, cells treated with taxanes are often arrested in the mitotic phase, unable to complete division.

Apoptosis:
* Ultimately, the disruption of mitosis and the prolonged mitotic arrest induced by taxanes trigger signals within the cell that lead to programmed cell death, or apoptosis. Cells undergoing mitotic arrest due to taxanes are unable to divide and survive, leading to their demise.

Question 12

What is the problem with Paclitaxel and why was Nab–Paclitaxel produced?

Vinca Alcaloids/Taxanes/Epothiolones

Answer 12

Paclitaxel is:
* poorly water soluble
* It is formulated with castor oil -(Cremophor EL)
* And uses ethanol as a vehicle.
* The Cremophor EL can cause significant hypersensitivity reactions

Nab-Paclitaxel is
* A nanoparticle albumin bound compound which negates the need for using Cremophor EL
* Markedly reducing the risk of hypersensitivity

Question 13

Name 1 Epothiolone?

Answer 13

Erubulin

Question 14

What is the mode of action of Epothilones?

Answer 14

Eribulin interferes with the growth of microtubules
interrupting the formation of mitotic spindles
leading to cellular death.

It is predominantly used in the treatment of breast cancer.

Question 15

How does each mitotic inhibitor/Tubulin inhibitor work?

Vinca Alcaloids/Taxanes/Epothiolones

Answer 15