Carcinogenesis and Chemotherapy

Question 1

What is the greatest cancer risk?

Answer 1

Aging

Question 2

What is the transformation of normal tissue into cancer cells called?

Answer 2

carcinogenesis

Question 3

What are four sources of carcinogenesis?

Answer 3

1. Natural radiation (cosmic, radon) 2. Environmental (benzopyrene in cigarette smoke, nitrates in good old hot dogs)
2. Viral transformation (Hep B risk for liver cancer, HPV to cervical cancer)
3. Spontaneous (immune failure)

Question 4

What is the mechanism for carcinogenesis?

Answer 4

Normal gene function transforms Suppressor genes subverted

Telomerase immortalize the bad cells

Question 5

Proto-oncogenes converted to oncogenes by mutations is an example of what?

Answer 5

transformation of normal gene function in carcinogenesis

Question 6

What is the name for the protective suppressor genes that get subverted in carcinogenesis?

Answer 6

Anti-oncogenes

Question 7

What is the two step process of carcinogenesis and is the order important?

Answer 7

1. Initiation (mutational injury)
2. Promotion (clonal expansion of injured cells)
   Initiation before promotion is critical

Question 8

How is a tumor cell different and the same as its host cell?

Answer 8

Different because mechanixm of growth control is absent.

Same biochemically to host tissue from which the tumor derived

Question 9

Is tumor cell growth endocrine or autocrine?

Answer 9

Autocrine, from growth factors secreted by itself

Question 10

What usually kills the patient?

Answer 10

The invasiveness of the tumor.

Question 11

Is the tumor fed from the same supply as the tissue it invades?

Answer 11

No, require independent nutrient/ O2 supply

Question 12

What are the three primary approaches for management of cancer?

Answer 12

1. Surgery
2. Radiation
3. Chemotherapy

Question 13

What is usually the first step for cancer treatment?

Answer 13

Surgical resection to decrease tumor burden

Question 14

What treatment is indicated for control of regional micrometastases and unresectable lesions?

Answer 14

Radiation

Question 15

Radiation and surgery both require what for treatment?

Answer 15

Tumor localization

Question 16

What is the treatment used for the systemic treatment of micrometastatic disease in other organs which can be used without surgery and radiation or in conjunction with surgery and radiation?

Answer 16

Chemotherapy

Question 17

What is the term for chemotherapy accompanying surgery and radiation?

Answer 17

Adjuvant therapy

Question 18

When is patient considered cured of cancer?

Answer 18

When 5 year disease free

Question 19

What does complete response/remission mean?

Answer 19

tumors gone

Question 20

What does partial response/ partial remission mean?

Answer 20

Tumor shrunk 50%

Question 21

What does “stable disease” mean with regards to cancer?

Answer 21

The tumor is neither growing nor shrinking

Question 22

What does “progressive disease” mean?

Answer 22

The tumor is growing

Question 23

After non-curative therapy, what is the character of the cancer once it returns?

Answer 23

Resistant to therapy

Question 24

What are the three chemotherapy regimens?

Answer 24

1. Induction therapy
2. Consolidation therapy
3. Maintenance therapy

Question 25

What is the term for chemotherapy that seeks rapid reduction in tumor cell burden?

Answer 25

Induction therapy

Question 26

What is the term for chemotherapy that seeks to complete or extend initial remission?

Answer 26

Consolidation therapy

Question 27

What is the term for chemotherapy that seeks to sustain the remission for as long as possible?

Answer 27

Maintenance therapy

Question 28

Watch and wait therapy is used mainly for what cancer type?

Answer 28

Slow growing cancer: leukemia, lymphoma, prostate

Question 29

Why is watch and wait therapy used on slow growing cancers?

Answer 29

The patient’s immune response may win Tumor is so slow growing, cancer drugs can’t target it The side Effects may outweigh benefits

Question 30

What are three risks associated with delaying cancer treatment?

Answer 30

Patients emotional well-being | Cancer may spread or transform rapidly Decrease likelihood of complete remission

Question 31

What is the ideal goal of cancer chemotherapy?

Answer 31

Eliminate all of tumor cell population with limited toxicity to patient

Question 32

A given concentration of drug, applied for a defined period of time, will kill a constant fraction of the cell population, independent of the number of cells is known as what?

Answer 32

Fractional cell kill hypothesis

Question 33

For a log kill of 2, which reduces the tumor cell number from 109 to 107, what percentage of the cell population must be killed?

Answer 33

99%

Question 34

What log kill is required to kill the total cell population?

Answer 34

Log Kill 9

Question 35

What is assumed with lower log kill numbers?

Answer 35

Immune system takes over to eradicate remaining cells

Question 36

What phase of the cell cycle do anti-neoplastic drugs focus on?

Answer 36

S-phase, M-phase

Question 37

What is occurring in S-phase?

Answer 37

DNA synthesis

Question 38

What is occurring in M-phase?

Answer 38

Cell division

Question 39

Of the S and M phases, which one is the major drug target?

Answer 39

S-phase

Question 40

Cells within solid tumors are normally in what phase?

Answer 40

G0 – dormant, insensitive to drugs

Question 41

What is a good thing about surgery or radiation that might aid chemotherapy?

Answer 41

Can recruit cells out of G0 back into active growth so they will be susceptible to drugs

Question 42

What is the clonal origin theory of tumors?

Answer 42

Every malignancy starts from 1 cell then forms a colony, that through mutations becomes heterogenous

Question 43

Why does the heterogeneity of tumor cells cause problems in treatment?

Answer 43

It makes them hard to target. One cell might have an efflux pump whil another cell is metabolically inactive.

Question 44

What is the problem when designing a cancer chemotherapy regimen?

Answer 44

cancer drugs have narrow therapeutic index which restricts simply increasing the dose

Question 45

What is a major type of resistance to cancer chemotherapy?

Answer 45

Multi-drug resistant pumps

Question 46

Why are liver cancers hard to treat (example of drug resistance of cancer)?

Answer 46

Liver cancer can enhance drug inactivation via the liver glutathione redox pathway

Question 47

What are nine ways cancer can be resistant?

Answer 47

1. Alter drug transport 2. Alter level or sensitivity of cell targets 3. Limited drug activation 4. Enhanced drug inactivation 5. Competition by endogenous substrates 6. Inability to undergo apoptosis 7. Mutations in growth arresting genes 8. Enhanced DNA repair 9. Autophagy

Question 48

What method can be used to circumvent cancer chemotherapy resistance?

Answer 48

combination chemotherapy (but this is susceptible to multi-drug resistant phenotype)

Question 49

Multi-drug resistant phenotype cancer s recognize what and pump it out?

Answer 49

large lipophylic naturally derived cancer drugs

Question 50

What are 5 types of cytotoxic drugs?

Answer 50

1. Alkylating agents 2. Antimetabolites 3. Antitumor antibodies 4. Mitotic inhibitors 5. Topoisomerase inhibitors

Question 51

Antimetabolites are analogues of what?

Answer 51

Natural substances or reaction intermediates

Question 52

Antimetabolites attack what cell cycle phase and do what?

Answer 52

Require metabolic activation then attack S-Phase to interfere with DNA synthesis

Question 53

Topoisomerase poisons are derived from what and do they require metabolic activation?

Answer 53

Natural (plant or bacteria). Do not require metabolic activation.

Question 54

Are topoisomerases cell cycle specific and how do they act?

Answer 54

Not cell-cycle specific, but active in the cell cycle. Promotes DNA strand breaks.

Question 55

Microtubule poisons are derived from what and active in what phase of the cell cycle, and do they require metabolic activation?

Answer 55

They are natural products, active in M-phase, and do not require metabolic activation

Question 56

Microtubule poisons act where in cancer cell?

Answer 56

interfere with microtubule function

Question 57

From what are alkylating agents derived?

Answer 57

They are chemically synthesized. First group of anti-tumor drugs.

Question 58

What are 2 types of alkylating agents?

Answer 58

Bifunction (DNA cross linkers) | Monofunction (DNA damager)

Question 59

Are alkylating agents cell cycle specific?

Answer 59

No

Question 60

What is a toxicity associated with alkylating agent usage?

Answer 60

Secondary malignancies

Question 61

Chemotherapy is toxic to what host tissues?

Answer 61

``` High growth fraction tissues Bone marrow Skin Hair follicles GI Sperm ```

Question 62

Of the high growth fraction tissues, which one is the dose limiter for chemotherapy?

Answer 62

Bone marrow

Question 63

What are the major chemotherapy side effects?

Answer 63

``` Nausea Stomatitis Alopecia Bone marrow suppression Organ toxicity ```

Question 64

When should chemo start?

Answer 64

Low tumor burden when growth fraction high

Question 65

How should chemotherapy be dosed?

Answer 65

Dose to maximum toxicity before changing therapy

Question 66

Should toxicity ever exceed therapeutic benefit?

Answer 66

No

Question 67

How to design combo therapy to obtain total cancer cell killing?

Answer 67

Use drugs with differing toxicity profiles, differing mechanisms of action, synergistic, and who don’t have common resistance

Question 68

What is the principle for cancer chemotherapy dosing?

Answer 68

Highest dose possible repeating does as frequently as tolerable

Question 69

Why treat cancer early?

Answer 69

1. Less metastases 2. More S-phase cells 3. More homogenous tumor 4. Fewer resistant tumor cells 5. Patient is healthier

Question 70

What is problem with animal testing cancer drugs?

Answer 70

It’s a mouse tumor(murine) or a human tumor in an immunosuppresed mouse, so it is not a direct correlation

Question 71

What is asked of a new cancer drug in phase III of human trials?

Answer 71

I"s the drug better than what is currently available"?