Cancer Therapeutics Flashcards
primary prevention
before exposure
secondary prevention
early detection (i.e. mammograms)
tertiary prevention
from onset of symptoms; treatment phase
alkylating agents
directly damage DNA to keep cell from reproducing; work in all phases of cell cycle
downside of alkylating agents
long-term damage to bone marrow
antimetabolites
interfere with normal cell function by substituting for normal building blocks of DNA/RNA; will damage cell during S phase (when DNA is copied)
examples of antimetabolites
topoisomerase inhibitors, mitotic inhibitors, proteasome inhibition
topoisomerase inhibitors
interfere with enzymes required to separate strands of DNA so they can be copied during S phase
mitotic inhibitors
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
mitotic inhibitors are usually _
plant alkaloids or derivations from natural products
proteasome inhibition
may prevent degradation of pro-apoptotic factors, permitting activation of programmed cell death in cancer cells dependent upon suppression of pro-apoptotic pathways
multi-drug resistance
increased expression of drug export pumps
drug detoxification
enzymatic detoxification of drug molecule
resistance to EGF-R inhibition
up-regulation of IGF-1R signaling amplification of Met gene or mutational activation of Ras gene
molecular targets for which targeted therapies exist
steroid receptors, HER2, ALK, CD20, bcr/abl, c-kit, hedgehog, RET, b-RAF
steroid receptors
for ER+ breast cancer, prostate cancer, and lymphoma
HER2
breast cancer
ALK
NSCLC
CD20
lymphoma
bcr/abl
CML
c-kit
GIST (GI stomach tumors)
hedgehog
basal cell and medullablastoma
RET
medullary thyroid cancer
b-RAF
melanoma
drug development pathway
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
where do new drugs come from?
serendipity, natural product screen, derivative of older agents, rational design based upon putative targets, repurposing
clinical trial phase 0
pharmacodynamics/kinetics
clinical trial phase I
screening for safety; 15-30 people
clinical trial phase II
efficacy against placebo; less than 100 people
clinical trial phase III
to compare the new treatment to the current standard (is it actually any better/less side effects); 100-1000 people
clinical trial phase IV
safety studies during sale
advantage of drug repurposing
safety proven, shorter development time, cheaper
