Cytotoxic Drugs

Question 1

What are the different parts of the cell cycle?

Answer 1

G0 to G1
G1 to S
S to G2 (DNA synthesis)
G2 to M

Question 2

What are the general characteristics of cell cycle specific chemo agents?

Answer 2

Tumour specific

Duration of exposure more important than dose

Question 3

What are examples of cell cycle specific chemo agents?

Answer 3

Antimetabolites; impairs nucleotide synthesis/ incorporation
Mitotic spindle inhibitors

Question 4

What are examples of antimetabolites?

Answer 4

Methotrexate:
Inhibits dihydrofolate reductase
6-Mercaptopurine/ cytosine arabinoside:
Incorporated into DNA
Hydroxyurea:
Impaired deoxynucleotide synthesis

Question 5

What are examples of mitotic spindle inhibitors?

Answer 5

Vinca alkaloids; vincristine/ vinblastine

Taxotere (taxol)

Question 6

What are the general characteristics of non-cell cycle specific agents?

Answer 6

Non-tumour specific; damage normal stem cells

Cumulative dose more important than duration

Question 7

What are examples of non-cell specific agents?

Answer 7

Alkylating agents
Platinum derivatives
Cytotoxic antibiotics

Question 8

What are examples of alkylating agents?

Answer 8

Chlorambucil/ melphalan

Bind covalently to bases of DNA and produce DNA strand breaks by free radical production

Question 9

What are examples of platinum derivatives?

Answer 9

Cisplatin

Carboplatin

Question 10

What are examples of cytotoxic antibiotics?

Answer 10

Anthracyclines; daunorubicin/ doxorubicin/ idarubicin

DNA intercalculation, impair RNA transcription, form free radicals via strand breaks in DNA

Question 11

What are the immediate side effects to cytotoxic drugs?

Answer 11

Bone marrow suppression
Gut mucosal damage
Alopecia

Question 12

What are examples of drug specific side effects?

Answer 12

Vinca alkaloids; neuropathy
Anthracyclines; cardiotoxicity
Cisplatin; nephrotoxicity

Question 13

What are some specific side effects to alkylating agents?

Answer 13

Infertility

Secondary malignancy

Question 14

What is the basis of combo chemo administration?

Answer 14

Non-cross resistant drug combos
Non-overlapping toxicity spectra
Additive/ synergistic mechanisms of action

Question 15

Why will chemo fail?

Answer 15

Slow tumour doubling time

Drug resistant mechanisms

Question 16

What are some common drug resistant mechanisms that cancers will adopt?

Answer 16

Decreased drug accumulation; MDR-1
Altered drug metabolism; cyclophosphamide
Increased DNA repair; cisplatin
Altered gene expression; reduced topoisomerase 2

Question 17

What limited intensive chemo?

Answer 17

Myelosuppression

Question 18

What can be done to overcome the myelosuppression associated with intensive chemo?

Answer 18

Haematopoietic growth factors
Combine myelosuppressive/ non-myelosuppressive agents
Intensify doses of active drugs (log-linear tumour kill) + stem cell rescue

Question 19

What are sources of stem cells for transplantation?

Answer 19

Blood vs bone marrow
Autologous
Allogeneic - sibling or unrelated

Question 20

What are the basic steps for stem cell transplantation?

Answer 20

Myeloablative therapy
Stem cell reinfusion
Bone marrow regeneration

Question 21

What is the specific treatment used for CML?

Answer 21

Targeted therapy with tyrosine kinase inhibitors

Question 22

What occurs in the G1 phase of the cell cycle?

Answer 22

Cell increases in size

Cellular contents duplicate

Question 23

What occurs in the S phase of the cell cycle?

Answer 23

DNA replication

Question 24

What occurs in the G2 phase of the cell cycle?

Answer 24

Cell prepares for division

Question 25

What occurs in the M phase of the cell cycle?

Answer 25

Mitosis followed by cytokinesis | Formation of 2 identical daughter cells

Question 26

What are the phases in the M cycle?

Answer 26

``` Prophase Metaphase Anaphase Telophase Cytokinesis ```

Question 27

What occurs in prophase?

Answer 27

Nucleolus disintegrates Nuclear membrane breaks down Spindle fibres appear

Question 28

What occurs in metaphase?

Answer 28

Chromosomes align at the metaphase plate

Question 29

What occurs in anaphase?

Answer 29

Centromeres divide | Sistem chromatids move to opposite poles

Question 30

What occurs in telophase?

Answer 30

Nuclear membrane reforms Chromosomes decondense Spindle fibres disappear

Question 31

What regulates the cell cycle?

Answer 31

Checkpoints

Question 32

What checkpoint is located at G1?

Answer 32

Restriction point (R)

Question 33

What will activation of the checkpoint result in?

Answer 33

Increased p53 production | p53 is a tumour suppressor gene that stops the cell cycle and starts repair mechanisms for damaged DNA

Question 34

What is the function of Rb in the cell cycle?

Answer 34

Restricts the ability of a cell to progress from G1 to S | CDK (cyclin dependent kinase) will phosphorylate it making it unable to restrict cell proliferation

Question 35

What cyclin is present at the G2 checkpoint?

Answer 35

Cyclin B | CDK 1

Question 36

What cyclin is present at the start of G1?

Answer 36

Cyclin D | CDK4

Question 37

What cyclin is present at the end of G1?

Answer 37

Cyclin E | CDK 2

Question 38

What cyclin in present in S?

Answer 38

Cyclin A | CDK2