l26 cancer

Question 1

t/f: cancer is the leading cause of death in Canada

Answer 1

t

Question 2

There are over _____ types of cancers

Answer 2

100

Question 3

metastasis

Answer 3

Cancer Characterized by abnormal cell growth with potential to spread to other parts of the body

Question 4

Causes of cancer (4)

Answer 4

1. Environmental and genetic factors
2. Tobacco, ionizing radiation, environmental pollution (asbestos, radon)
3. Viral infections (HIV with Hodgkin’s and Non-Hodgkin’s lymphoma; human papilloma virus with cervical cancer)
4. Genetics (BRCA 1 in breast cancer)

Question 5

Cancer is fundamentally a disease of cell _____ regulation. It arises when genes that regulate cell growth are _____

Answer 5

Growth; mutated

Question 6

Cell cycle definition

Answer 6

Series of events leading to duplication of DNA and division of cytoplasm to produce two daughter cells

Question 7

cell cycle phases

Answer 7

1. GI phase: checkpoint to ensure cell ready for DNA synthesis
2. S phase: DNA synthesis
3. G2 phase: checkpoint to ensure cell ready for mitosis
4. M phase: mitotic phase (cell divides into two daughter cells)
5. G0 phase: quiescent state

Question 8

Genes important to the regulation of cell cycle are divided into which two groups?

Answer 8

Tumour suppressor genes and oncogenes

Question 9

Tumour suppressor genes

Answer 9

Both these genes and the proteins they encode repress cell cycle or promote apoptosis by:
inhibiting cell division;
initiating apoptosis following irreversible DNA damage;
DNA repair proteins (BRCA)

Question 10

p53

Answer 10

tumour suppressor protein that regulates cell cycle; mutated in 50% of all tumours

Question 11

Proto-oncogenes

Answer 11

normal genes involved in cell growth and proliferation or inhibition of apoptosis

Question 12

oncogenes produced by

Answer 12

Mutations (point mutations, chromosomal translocation) can increase expression

Question 13

Point mutations

Answer 13

Small-scale deletions or insertions which effect expression

Question 14

Chromosomal translocation

Answer 14

When to separate chromosomal regions become abnormally fused

Question 15

Philadelphia chromosome

Answer 15

Specific genetic abnormality in chromosome 22 found in leukaemia cancer cells (abnormal translocation of chromosome 9 and 22)

Broken end of chromosome 22 contains the BCR Gene which fuses with a fragment of chromosome 9 that contains the ABL1 gene

Fusion creates a new Gene: BCR-ABL

Question 16

Philadelphia chromosome leads to

Answer 16

unregulated expression of protein tyrosine kinase activity leading to unregulated cell cycle and cell division

Question 17

t/f: usually multiple oncogenes and mutated tumour suppressor genes will act in concert to cause cancer

Answer 17

t

Question 18

t/f: 1/3 of cancer patients are cured with local treatment strategies (surgery, radiotherapy)

Answer 18

t

Question 19

t/f: anticancer drugs alone cure a majority of all cancer patients in tumour is diagnosed at Advanced stage; why

Answer 19

f: anticancer drugs alone cure less than 10% of all cancer patients when tumour is diagnosed at Advanced stage (usually given in combination surgery and radiation)

Question 20

How do anti-cancer drugs interfere with cell cycle? (2)

Answer 20

Some anti-cancer drugs act at specific phases in the cell cycle, mainly at the S and M phase

other drugs are cytotoxic at any point in the cell cycle (ex: estrogen receptor antagonist tamoxifen)

Question 21

Tumour cells generally have a _____ (lower/higher) percentage to proliferating cells than normal cells, so are (more/less) susceptible to S&M phase anticancer drugs

Answer 21

Higher; more

Question 22

t/f: normal tissues that proliferate rapidly (bone marrow, hair follicles, intestinal epithelium) are more susceptible to damage from cytotoxic drugs

Answer 22

t

Question 23

t/f: few categories of medication have a narrower therapeutic index and Greater potential for causing harmful effects than anti cancer drugs

Answer 23

t

Question 24

four bases form DNA:

Answer 24

two pyrimidines (thymine and
cytosine) and two purines
(guanine and adenine)

Question 25

RNA incorporates _ | instead of thymine

Answer 25

uracil

Question 26

•pyramidine analogues compete with | normal__ precursors for the enzyme __

Answer 26

``` pyrimidines thymidylate synthase (TS) ```

Question 27

•TS required for the conversion of __ to __ (i.e. | thymine+deoxyribose sugar)

Answer 27

dUMP to dTMP

Question 28

example of pyrimidine analogue, what happens

Answer 28

5-fluorouracil (5-FU) •inactive in its parent form and requires activation to active metabolite FdUMP

Question 29

__ inhibits purine nucleotide biosynthesis and metabolism by inhibiting an enzyme called __ rate limiting factor for purine synthesis, alters the synthesis and function of RNA and DNA

Answer 29

6-mercaptopurine; | phophoribosyl pyrophosphate amidotransferase (PRPP amidotransferase);

Question 30

•Alkylating agents are highly __ compounds which__ link to chemical groups (phosphates, amines, sulfhydryl and hydroxyl groups) commonly found in _ _ •Lead to __ between strands of DNA and strand__

Answer 30

``` reactive covalently nucleic acids cross-linking breakage ```

Question 31

_ particularly susceptible to the formation of covalent bond with alkylating agents

Answer 31

N7 atom of guanine

Question 32

cancer cells are most | susceptible to Alkylating Agents are in __ stage of cell cycle

Answer 32

G1 and S | phases

Question 33

Alkylating Agents example: | • i.e. Cisplatin

Answer 33

platinum analogue • lead to inter-strand crosslinks leading to inhibition of DNA synthesis and function

Question 34

Folic acid is an essential _ _ that is converted by enzymatic_ to_ _ provide_ groups for the synthesis of precursors of_ and_ (thymine or uracil).

Answer 34

dietary factor reduction FH4 cofactors methyl DNA, RNA

Question 35

Folic acid analogues interfere | with

Answer 35

FH4 metabolism thereby | inhibiting DNA replication

Question 36

Anti-folates: methotrexate folic acid _ that bind with _ affinity to the active catalytic site of _ _ effective during _ phase and are most effective when cells are proliferating _

Answer 36

folic acid analogue that bind with high affinity to the active catalytic site of dihydrofolate reductase effective during S phase and are most effective when cells are proliferating rapidly

Question 37

Vinca Alkaloids * derived from * inhibit _ polymerization * disrupts the assembly of _ involved in _ _ _ (_ phase)

Answer 37

derived from the periwinkle plant (Vinca rosea) • inhibit tubulin polymerization •disrupts the assembly of microtubules involved in mitotic spindle apparatus (M phase)

Question 38

Taxanes * derived from * promote __ assembly through _ affinity binding * inhibits _ and _ _ (_ phase) * i.e. __

Answer 38

* derived from the Pacific yew tree (Taxus brevifolia) * promote microtubule assembly through high affinity binding * inhibits mitosis and cell division (M phase) * i.e. paclitaxel

Question 39

Camptothecins • derived from the • DNA topoisomerases are nuclear enzymes that __ _ stress in _ DNA (through _ _ and _) • Camptothecins bind and _ the normally transient DNA–topoisomerase _ _. • Although the _ _action of topoisomerase is not affected, the _ step is inhibited, leading to the accumulation of __ breaks in DNA • These are _-phase specific drugs because ongoing _ _ is necessary for cytotoxicity

Answer 39

• derived from the Camptotheca acuminata tree • DNA topoisomerases are nuclear enzymes that reduce torsional stress in supercoiled DNA (through strand breakage and resealing) • Camptothecins bind and stabilize the normally transient DNA–topoisomerase I complex. • Although the initial cleavage action of topoisomerase is not affected, the re-ligation step is inhibited, leading to the accumulation of single-stranded breaks in DNA • These are S-phase specific drugs because ongoing DNA synthesis is necessary for cytotoxicity

Question 40

Antibiotics products of the soil microbe _ bind DNA through _, block DNA _ and cell _

Answer 40

products of the soil microbe Streptomyces bind DNA through intercalation, block DNA synthesis and cell replication

Question 41

``` Antibiotics • i.e.: Anthracyclines (doxorubicin) • _ widely used anti-cancer drug • 4 mechanisms of action: 1.inhibit _ 2.generate __ _ (DNA _) 3._ affinity binding to DNA 4.bind _ membrane to alter _ and _ transport ```

Answer 41

Antibiotics ``` • i.e.: Anthracyclines (doxorubicin) • most widely used anti-cancer drug • 4 mechanisms of action: 1.inhibit topoisomerases 2.generate free radicals (DNA mutagenesis) 3.high affinity binding to DNA 4.bind cellular membrane to alter fluidity and ion transport ```

Question 42

tyrosine kinase inhibitors (i.e. imantinib) •inhibits the _ _ _of the _ _ •treat _

Answer 42

``` tyrosine kinase inhibitors (i.e. imantinib) •inhibits the tyrosine kinase domain of the Bcr-Abl oncoprotein •treat leukemia ```

Question 43

epidermal growth factor receptor (EGFR) inhibitors ``` • EGFR is _-expressed in a number of _ tumors • Activation of EGFR promotes _ _ and _, _, and _, and _ • i.e. Cetuximab is a _ _ directed against the _ domain of EGFR ```

Answer 43

``` epidermal growth factor receptor (EGFR) inhibitors • EGFR is over-expressed in a number of solid tumors • Activation of EGFR promotes cell growth and proliferation, invasion, and metastasis, and angiogenesis • i.e. Cetuximab is a monoclonal antibody directed against the extracellular domain of EGFR ```

Question 44

``` •hormonal anti-cancer agents •i.e.: tamoxifen • selective _ receptor antagonist •blocks binding of _ to _ sensitive cancer cells in breast tissue ```

Answer 44

``` •hormonal anti-cancer agents •i.e.: tamoxifen • selective estrogen receptor antagonist •blocks binding of estrogen to estrogen sensitive cancer cells in breast tissue ```

Question 45

Primary Resistance:

Answer 45

develops spontaneous in the absence of prior | exposure to anti-cancer drugs (i.e. p53 mutations)

Question 46

Acquired Resistance:

Answer 46

develops in response to a given anticancer agent

Question 47

Adverse Effects - 4

Answer 47

``` • dose related • occur primarily in rapidly growing tissues, such as bone marrow, intestinal mucosa, and reproductive system • symptoms include impaired immune system, diarrhea, hair loss, nausea and vomiting • many anti-cancer drugs are carcinogenic in nature, thus increased risk of secondary malignancies ```