Dugga 3 - Anticancer

Question 1

When are cancer cells formed?

Answer 1

When normal cells lose the normal regulatory mechanisms that control growth and multiplication

Question 2

What is a loss of differentiation?

Answer 2

When cancer cells become rogue and lose their specialised characteristics that distinguish one cell from another

Question 3

What does neoplasm mean?

Answer 3

New growth, and is a more accurate term for cancer but not used. Tumour actually means swelling

Question 4

What does it mean that a cancer is benign?

Answer 4

That it is localised

Question 5

What does malignant mean?

Answer 5

When a cancer invades other parts of the body through metastasis

Question 6

What is carcinogenesis?

Answer 6

The beginning of cancer

Question 7

Some cancers are caused by virus, mention some

Answer 7

HPV (human papillomavirus), hepatitis B and HIV

Question 8

What are protooncogenes?

Answer 8

Genes that normally code for proteins involved in the control of cell division and differentiation

Question 9

What is an oncogene?

Answer 9

A protooncogene that is mutated and disrupts the normal function

Question 10

What is the Ras protein?

Answer 10

Involved in the signalling pathway leading to cell division

Mutations of the Ras gene are present in 20-30 % of human cancers

Question 11

What are tumour suppression genes?

Answer 11

Genes that code for proteins that are involved in these processes of checking, repair and suicide

TP53 an example and codes for the protein p53

Question 12

Genetic defects can lead to which cellular defects?

Answer 12

Abnormal signalling pathways
insensitivity to growth inhibitory signals
Abnormalities in cell cycle regulation
Evasion of programmed cell death
Limitless cell division
Ability to develop new blood vessels
Tissue invasion and metastasis

Question 13

What is apoptosis?

Answer 13

Programmed cell death

Question 14

What is angiogenesis?

Answer 14

developing new blood vessels

Branching and extensions of existing capillaries

Question 15

Do most if not all of these defects have to happen for cancer to be malignant?

Abnormal signalling pathways
insensitivity to growth inhibitory signals
Abnormalities in cell cycle regulation
Evasion of programmed cell death
Limitless cell division
Ability to develop new blood vessels
Tissue invasion and metastasis

Answer 15

Yes

Question 16

What are integrins

Answer 16

Present on the surface of new blood vessels and absent on mature vessels. They protect new cells from apoptosis

Question 17

Is inhibiting angiogenesis a way to tackle cancer?

Answer 17

Yes, and less toxic than traditional chemotherapy. Not used on their own but in combination with surgery, chemotherapy or radiation

Question 18

Which other way can leaky blood vessels be targeted in battling cancer?

Answer 18

Drugs encapsulated in liposomes and nanospheres are too big to escape from normal blood vessels but will escape from leaky blood vessels and concentrate in the tumour cell

Question 19

Why is it an issue that some tumour cells cannot receive blood supply?

Answer 19

They become dormant and cannot be reached by anticancer therapy. When cancer treatment is stopped the dormant cells start multiplying and the tumour reappers. It has been observed that such cells are more likely to metastasise

Question 20

What is hypoxia?

Answer 20

Insufficient blood supply and lack of oxygen

Question 21

Why is the environment around the tumour more acidic?

Answer 21

Because the lack of oxygen means that tumour cells are forced revert to glycolysis to produce energy. That leads to acidic byproducts within the cell. They export these acidic protons to the extracellular space.

Question 22

What is a prophylactic?

Answer 22

A way of preventing disease

Question 23

What prophylactic could be used to prevent cancer in susceptible individuals

Answer 23

Angiogenesis inhibitors

Question 24

Which are important anticancer agents?

Answer 24

Agents that inhibit the polymerisation and depolymerisation of microtubules

Question 25

Give examples of what binds to tubulin and inhibit polymerisation process

Answer 25

Vinca alkaloids, podophyllotoxin, combretastatins, other natural products

Question 26

What does Paclitaxel do?

Answer 26

Bind to tubulin and accelerate polymerisation by stabilising the resulting microtubules

Question 27

What are tyrosine kinase inhibitors?

Answer 27

Selective against receptor tyrosine kinase targets which affect survival of cancer cells

Question 28

What is gefinitib?

Answer 28

A kinase inhibitor used to treat lung cancer

Question 29

Which different kinase inhibitors exist?

Answer 29

cycin-dependent kinase inhibitors (CDK) Inhibitors of the MAPK signal transduction pathway (target B Raf) Inhibitors of PI3K-PIP3 pathways Janus kinase Multi-receptor tyrosine kinase inhibitors Inhibitors of ALK Inhibitors of RET and KIF5B-RET

Question 30

Do cancers overexpress proteins involved in signalling pathways stimulating growth and division?

Answer 30

Yes

Question 31

Is the abnormal form of Ras associated with many cancers?

Answer 31

Yes

Question 32

What are protein kinases?

Answer 32

Enzymes using ATP to phosphorylate hydroxyl or phenol groups

Question 33

How do kinase inhibitors work?

Answer 33

Bind to the ATP binding region and other regions of the active site

Question 34

What are metalloproteinases?

Answer 34

Zinc-dependent enzymes that play an important role in invasiveness and metastasis of cancer. Catalyse cleavage of peptide bonds in protein substrates.

Question 35

What are four main groups of MMPs (matrix metalloproteinases)

Answer 35

Collagenases Gelatinases Stromelysins Membrane type

Question 36

What are MMPIs? (Matrix metalloproteinase inhibitors) And how are they useful?

Answer 36

Inhibit the breakdown of extracellular matrix to make it difficult to cancers to metastasise and spread

Question 37

What are proteasome inhibitors?

Answer 37

Proteasomes eliminate damaged or misfolded proteins. Proteasomes destroy cells marked with ubiquitin. Inhibiting proteasomes in cancer cells could be useful in order to trigger apoptosis in cancer cells

Question 38

How do MMPs work (matrix metalloproteinases) and why would be be good to inhibit them?

Answer 38

Zinc-dependent enzymes degrade the extracellular matrix and encourage angiogenesis, tumour propagation and metastasis

Question 39

What are histone acetylases and deacetylases involved in?

Answer 39

Regulation of transcription

Question 40

How are monoclonal antibodies used?

Answer 40

Targeted against antigens which are overexpressed in certain cancer cells. Useful in treating breast cancer, colorectal cancer and lymphomas

Question 41

What is an antibody drug conjugate and how can it be used?

Answer 41

Linking a highly potent drug or radioisotope to an antibody. Will target specific cancer cells and drug would be released inside the cell after being enveloped

Question 42

How can drugs be attached to antibodies?

Answer 42

Via lysine residues. Or the antibody can be made to produce thiol or aldehyde groups to which the drug can be attached

Question 43

What is ADEPT?

Answer 43

An antibody-enzyme conjugate which is targeted to specific cancer cells. Once the antibody is attached to a cancer cell, a prodrug is administered which is activated by the enzyme at the tumour site

Question 44

WHat is ADAPT?

Answer 44

Antibody that has catalytic activity designed to activate a prodrug

Question 45

WHat is GDEPT?

Answer 45

The delivery of a gene to a cancer cell. The genes code for enzymes capable of activating an anticancer prodrug

Question 47

Give examples of alkylating agent

Answer 47

Cisplatin. Works on nucleic acids. React with nucleophile, forms covalent bonds. Nitrogen mustard was first

Question 48

Give example of intercalation agent

Answer 48

Anthracycline Doxirubicin Idarubicin Can slip into DNA and distort structure

Question 49

Give example of antimetabolite

Answer 49

Methotrexate (no severe side effects, can be used life long, can be user antibiotics) Acts on enzymes Similar to folic acid and inhibit formation of FH4

Question 50

Give example or hormone based

Answer 50

Prednisolone Against hormone dependent cancers

Question 51

Give example of inhibitors of tubulin polymerisation

Answer 51

Vinblastine

Question 52

Give example of inhibitors of tubulin depolymerisation

Answer 52

Paclitaxal

Question 53

Give example of inhibitors or signaling pathway

Answer 53

Lonafarnib (Ras) Gefitinib (protein kinase)