Cancer Pharmacology (Part 1 of 2)

Question 1

What are oncogenes?

Answer 1

genes that positively influence tumor formation/ cell growth

Question 2

what is an example of an oncogene?

Answer 2

Ras

Question 3

what is a tumor suppressor gene?

Answer 3

genes that negatively impact tumor growth

Question 4

what is an example of a tumor suppressor gene?

Answer 4

p53

Question 5

how would you know whether a gene is an oncogene or a tumor suppressor?

Answer 5

oncogenes promote cell growth while tumor suppressor genes slow growth

Question 6

the majority of cells in our bodies are at what phase of the cell cycle?

Answer 6

G0 “resting”

Question 7

what is the purpose of cell cycle checkpoints?

Answer 7

they control transitions between cell cycle stages

Question 8

what is being checked at cell cycle checkpoints?

Answer 8

is there DNA damage? is there spindle assembly? are there favorable conditions? is there completed replication?

Question 9

what happens if there is failure to pass a cell cycle checkpoint?

Answer 9

the cell cycle is delayed or cell apoptose

Question 10

aberrations in checkpoint regulation result in what?

Answer 10

uncontrolled and unregulated cell proliferation

Question 11

activation of oncogenes has what result?

Answer 11

it overrides G1 arrest

Question 12

inactivation of tumor suppressor genes has what result?

Answer 12

overrides G2 arrest

Question 13

what are the indications for primary chemotherapy?

Answer 13

when the cancer is advanced, no alternative treatment exists, or it is an advanced metastatic disease

Question 14

primary chemotherapy can cure some cancers- what are they?

Answer 14

hodgkin’s and non-hodgkin’s lymphoma, choriocarcinoma, germ cell cancer, and AML

Question 15

what is neoadjuvant chemotherapy?

Answer 15

the use of chemotherapy in patients who present with localized cancer for which alternative local therapies, such as surgery, exist, but which have been shown to be less than completely effective

Question 16

what is the goal of neoadjuvant chemotherapy?

Answer 16

to reduce the size of the primary tumor

Question 17

what is adjuvant chemotherapy?

Answer 17

when additional chemotherapy is given for a defined period of time after surgery–> helps to prevent relapse

Question 18

what are the goals of adjuvant chemotherapy?

Answer 18

to reduce the incidence of local and systemic recurrence

Question 19

what is tissue growth fraction?

Answer 19

the ratio of proliferating to G0 cells

Question 20

as a general rule, antineoplastic agents are more effective on?

Answer 20

cells with a high growth fraction; and they will impact noncancerous high growth cells

Question 21

what are some examples of cells with high growth fraction?

Answer 21

cells of the bone marrow, GI tract, hair follicles, and sperm-forming cells

Question 22

what is one significant determinant of responsiveness to chemotherapy?

Answer 22

the growth fraction

Question 23

as the tumor burden increases, what happens to the growth fraction and the doubling time?

Answer 23

the growth fraction decreases and the doubling time increases

Question 24

the initial growth rate of most solid tumors is what?

Answer 24

rapid but decreases over time

Question 25

why is a low growth fraction in tumors challenging?

Answer 25

because chemotherapy will have minor activity

Question 26

the growth fraction of solid tumors can be increased how?

Answer 26

by reducing the tumor burden (i.e. surgery or radiation)

Question 27

what does the log cell kill hypothesis allow us to better understand?

Answer 27

the impact of the effect that a single dose has on the cancer cells: it's a fraction of cells rather than an absolute number- so in each individual treatment, you can expect to kill a fraction of the cells that are remaining

Question 28

antineoplastic therapy follows what kinetics? and what does this mean?

Answer 28

first-order; this means that a given dose of drug destroys a constant fraction of cells

Question 29

what is the approach to the eradication of cancer like?

Answer 29

it is a step-wise approach

Question 30

what are common routes of administration of antineoplastic drugs?

Answer 30

IV and PO

Question 31

what are the benefits of alternative routes of administration of antineoplastic drugs?

Answer 31

they can reduce systemic toxicity and increase drug delivery (by avoiding pharmacologic sanctuaries)

Question 32

what are pharmacological sanctuaries?

Answer 32

regions where tumor cells are less susceptive to antineoplastic agents

Question 33

what are some examples of alternative routes of administration of antineoplastic drugs?

Answer 33

intracavity, intrathecal, intraventricular, intraarterial, topical, and isolated limb perfusion

Question 34

combination drug therapy is more successful than single-agent regimens; what are the advantages of combination chemotherapy?

Answer 34

it provides maximal cell killing within the range of tolerated toxicity; it is effective against a broader range of cell lines in a heterogenous tumor population and it may delay or prevent the development of drug-resistant tumors

Question 35

what is primary/inherent chemotherapeutic resistance?

Answer 35

drug resistance in the absence of prior exposure to available standard agents

Question 36

what is the main contributor to primary/inherent chemotherapeutic resistance?

Answer 36

the genomic instability (i.e. p53 mutations)

Question 37

what is acquired chemotherapeutic drug resistance?

Answer 37

develops in response to exposure to a given cancer chemotherapeutic drug

Question 38

what genetic change is occurring in cases of acquired chemotherapeutic drug resistance?

Answer 38

amplification or suppression of a particular gene

Question 39

how does the increasing heterogeneity of cancers over time affect treatment plan?

Answer 39

as the different cell lineages within the cancer cell changes, it affects our ability to kill and target those cancers

Question 40

what is p-glycoprotein (PGP) and where is it expressed?

Answer 40

it is expressed in tissues with barrier functions, such as the kidneys, liver, and GI tract; it does a really good job of taking drugs that are inside the cell and kicking them out

Question 41

what does a high baseline expression of PGP correlate with?

Answer 41

correlates with primary/inherent resistance to natural products; PGP can also be over-expressed leading to acquired drug resistance

Question 42

many antineoplastic agents are mutagens themselves- what does this mean? and give an example

Answer 42

they can give rise to neoplasms years after treatment (e.g. alkylating agents have cause AML and ALL)

Question 43

what are common adverse effects of antineoplastic agents?

Answer 43

nausea, vomiting, fatigue, stomatitis, and alopecia; myelosuppression, low sperm count, and depressed development of exposed children

Question 44

what can myelosuppression lead to?

Answer 44

can lead to impaired wound healing and predisposition to infection

Question 45

what agents are used as rescue agents for neutropenia, thrombocytopenia, and anemia?

Answer 45

hematopoietic agents

Question 46

what agents are used as rescue agents for emetogenic effects?

Answer 46

serotonin receptor antagonist (ondansetron)

Question 47

what agents are used as rescue agents to delay skeletal complications?

Answer 47

bisphosphonates