Cancer Therapeutics

Question 1

primary prevention

Answer 1

before exposure

Question 2

secondary prevention

Answer 2

early detection (i.e. mammograms)

Question 3

tertiary prevention

Answer 3

from onset of symptoms; treatment phase

Question 4

alkylating agents

Answer 4

directly damage DNA to keep cell from reproducing; work in all phases of cell cycle

Question 5

downside of alkylating agents

Answer 5

long-term damage to bone marrow

Question 6

antimetabolites

Answer 6

interfere with normal cell function by substituting for normal building blocks of DNA/RNA; will damage cell during S phase (when DNA is copied)

Question 7

examples of antimetabolites

Answer 7

topoisomerase inhibitors, mitotic inhibitors, proteasome inhibition

Question 8

topoisomerase inhibitors

Answer 8

interfere with enzymes required to separate strands of DNA so they can be copied during S phase

Question 9

mitotic inhibitors

Answer 9

stop mitosis in M phase of cell cycle but can damage cells in all phases by keeping enzymes from making proteins needed for cell reproduction

Question 10

mitotic inhibitors are usually _

Answer 10

plant alkaloids or derivations from natural products

Question 11

proteasome inhibition

Answer 11

may prevent degradation of pro-apoptotic factors, permitting activation of programmed cell death in cancer cells dependent upon suppression of pro-apoptotic pathways

Question 12

multi-drug resistance

Answer 12

increased expression of drug export pumps

Question 13

drug detoxification

Answer 13

enzymatic detoxification of drug molecule

Question 14

resistance to EGF-R inhibition

Answer 14

up-regulation of IGF-1R signaling amplification of Met gene or mutational activation of Ras gene

Question 15

molecular targets for which targeted therapies exist

Answer 15

steroid receptors, HER2, ALK, CD20, bcr/abl, c-kit, hedgehog, RET, b-RAF

Question 16

steroid receptors

Answer 16

for ER+ breast cancer, prostate cancer, and lymphoma

Question 17

HER2

Answer 17

breast cancer

Question 18

ALK

Answer 18

NSCLC

Question 19

CD20

Answer 19

lymphoma

Question 20

bcr/abl

Answer 20

CML

Question 21

c-kit

Answer 21

GIST (GI stomach tumors)

Question 22

hedgehog

Answer 22

basal cell and medullablastoma

Question 23

RET

Answer 23

medullary thyroid cancer

Question 24

b-RAF

Answer 24

melanoma

Question 25

drug development pathway

Answer 25

identification of potential target --> validate whether this target will actually have impact --> HTS to identify targeting hit drugs --> further refinement to pick the hit that will have most effect --> enhance potency --> animal test --> clinical test

Question 26

where do new drugs come from?

Answer 26

serendipity, natural product screen, derivative of older agents, rational design based upon putative targets, repurposing

Question 27

clinical trial phase 0

Answer 27

pharmacodynamics/kinetics

Question 28

clinical trial phase I

Answer 28

screening for safety; 15-30 people

Question 29

clinical trial phase II

Answer 29

efficacy against placebo; less than 100 people

Question 30

clinical trial phase III

Answer 30

to compare the new treatment to the current standard (is it actually any better/less side effects); 100-1000 people

Question 31

clinical trial phase IV

Answer 31

safety studies during sale

Question 32

advantage of drug repurposing

Answer 32

safety proven, shorter development time, cheaper