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Cancer > Cancer Part 3 > Flashcards

Cancer Part 3 Flashcards

1
Q

what are the two types of plant alkaloids?

A

microtubule inhibitors
Topoisomerase inhibitors

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2
Q

What are the 2 types of microtubule inhibitors?

A

Vinca Alkaloids
Taxanes

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3
Q

What are the type of Vinca Alkaloids and what is it used for?

A

Vincristine: Childhood ALL, Wilm’s tumour, Lymphomas
Vinblastine: With Bleomycin/Cisplatin for metastatic testicular carcinoma and Lymphomas
Vinorelbine: Non-small cell lung cancer

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4
Q

what is the general mechanism of spindle fibre formation during anaphase?

A

spindle fibres formed by tubulin dimers (alpha and beta)- GTP binds and causing GTP dependant reaction causing polymerisation.

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5
Q

How to vinca alkaloids causes DNA damage

A

Vinca alkaloids inhibits GTP-dependent binding of the alpha and beta tubulin.

prevents the spindle fibres from forming.

During metaphase, the chromatids are not separated and are therefore frozen in time.

This failure to progress can lead to apoptosis.

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6
Q

What are some side effects of vinca alkaloids?

A

N/V/D (especially vincristine)
Alopecia
Extravasation

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7
Q

What are some side effects that are specific to vinblastine?

A

Myelosuppression- bone marrow suppression

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8
Q

What are some side effects that are specific to vincristine?

A

Peripheral neuropathy

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9
Q

What is the general mechanism of TAXANES?

A

Taxanes work by preventing the depolymerisation of the microtubules.

By making the spindle fibres EXTRA stable they are unable to draw the sister chromatids to either pole of the cell.

The cell is then permanently stuck in metaphase and the cell cycle is unable to continue.

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10
Q

What are some examples of taxanes?

A

paclitaxel
docetaxel
Taxotere

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11
Q

What are the 4 binding sites found on the microtubules?

A

Vinca binding site
Colchicine binding site
Laulimalide binding site
Taxanes binding site

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12
Q

What is HALICHONDRIN B?

A

A natural occurring ANTITUBULIN agent found in rare Japanese sponges.

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13
Q

what is ERIBULIN?

A

is a synthetic analogue of potent anti-tubulin agent HALICHRONDRIN B.

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14
Q

What is the general moa of ERIBULIN?

A

Microtubule inhibitors, specifically inhibit the microtubule growth.

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15
Q

What is ERIBULIN usually used to treat?

A

Breast Cancer (Third Line treatment)

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16
Q

What are some side effects linked to Eribulin?

A

low incidence of peripheral neuropathy.
Neutropenia
Fatigue

17
Q

What is the use of topoisomerase?

A

Used to cleave the DNA strand and unwind them so DNA polymerisation can occur. It can also be used to relax DNA strands that are supercoiled.

18
Q

what are the two types of topoisomerases and their use?

A

Topoisomerase 1- cuts only ONE dna strand and allows it to relax and unwind.

Topoisomerase 2: cuts both DNA strands and allows both to unwind

in both cases the DNA strand is broken and reformed

19
Q

How do topoisomerase inhibitors work

A

> Topisomerase inhibtiors prevent the DNA strand from being reformed once cut by the Topoisomerase.

> TOPO-INHIBITORS form a bond in between the exposed DNA base groups. This weakens the DNA chain and leads to double strand break— cell death

20
Q

What are some examples of topo 1 inhibitors?

A

Topotecan, Irinotecan

21
Q

What are some examples of Topo2 inhibitors?

A

Etoposide Anthracyclines
Doxorubicin’s

22
Q

Characteristics of of Plant alkaloids

A

High MW
Highly Lipophilic

23
Q

Name a microtubule inhibitor that is taken orally

A

VERU-111 aka Sabizabulin

24
Q

What is VERU-111 currently being used for

A

Trials for Advanced prostate and breast cancer

25
Q

What is the MOA of VERU-111

A

Microtubule inhibitors targeting the colchicine-binding site

26
Q

What are the benefits of Microtubule inhibitors targeting the colchicine-binding site

A

Less vulnerable to resistance

27
Q

What is the function of Etoposide

A

Blocks strands religation

Cancer (18 decks)

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