Cancer therapeutics Flashcards
Paclitaxel MOA
Neuropathy caused by blocking __
cisplatin MOA
belomycin MOA
stabilizes microtubules
transport of NT
cross link/alkylate DNA
intercalates DNA
PARP inhibitor ____
Many women have __/__ BC, while others are ___
BRCA fxns w___, __ is backup
Olaparib inhibit ___, approved for ___ OC that has failed w __ or __ or __
olaparib
BRCA1/2, BRCA-
DNA repair proteins, PARP
polyADP ribose poly, BRCA-, taxanes/platins/anthracyclines
Etoposide inhibits ___ and leaves enzyme bound to ___
in kids, can cause unusual form of ____
Topo2, broken DNA
acute nonlymphocytic leukemia
Some cancer pts lose __ w treatment
young men may have more __ in early stages of development than ___
potential strategy is to ___ sperm/oocyte/embryo prior to tx (aka __)
another is to inhibit ___ or ____ during tx
fertility
sperm, older men
freeze, cryopreservation
spermatogenesis, follicular development
__ status is important in tx
chemotherapy can be added for ___ER+ tumors
Tamoxifen inhibits ___
ER+ tumors become resistant to __
one mechanism is by activating the ___ to __ to __ pathway
an ___ substrate can phosphorylate ___, leading to activation w/out a __
BRCA1/2
stage 3
ER
PI3K-Akt-mTOR
mTOR, ER, ligand
Everolimus inhibits ___, important for metab and __ signalling
used in conjxn w hormonal agents like __ or ___ and for resistance in ___ BC
__ gene is freq amplified in BC
__ inhibitors freq __
__ can phosphorylate ___ and activate it in an ___ manner
Cyclin dependent CDK can be inhib w ___
mTOR protein kinase, survival
exemestance, anastrazole, ER+
cyclin D1
CDK, repressed
CDK, ER, ligand-independent
palbociclib
doxorubin can cause __
within a tumor, mutations can change resistance to ___ or changes in ___
small numbers of ___ survive tx and can become ___
Drug efflux pumps
Critical drug transport events include ___ and ___ and ___
proteins affect ___ as well as ___
substrates include P, D, V, E
__ and __ are not p glycoprotein substrates
cardiotoxicity
specific targets (ie topo2), drug kinetics
cancer cells, drug resistant
MDR1, p glycoprotein, MRP1
uptake of drug, retention
Paclitaxel, doxorubicin, vincristine, etoposide
cytarabine/mtx
Drug resistance mechs
Alkylating agents: inc __ and inc ___, inc ___ leading to inactivation
MTX: resistancefrom inc __ and __ in DHFR, as well as changes in __ and ___ (highly active derivative)
w/ her2neu cancer, want to add __
DNA repair, permeability of drug, glutathione prodxn
synth/mutations, drug transport/polyglutamate formation
trastuzumab
Ado trastuzumab emtansine is __ bound to __, which inhibits ___
__ is a monoclonal Ab targeting a different portion of ___
__ is a __ of HER2
results in inhibition of ___
trastuzumab, DM1, microtubule dynamics
Pertuzumab, HER2R
Lapatinib, small molecule inhibitor, multiple receptors
__ is a RF for triple neg BC
___ limits effectiveness of chemo and ___
causes __ which drives ___
__ can inc insulin levels, acting as a ___`
obesity
obesity, survival
inflammation, signaling
insulin resistance, survival signal
drugs that modify/bind DNA (3)
target = ___
drugs that inhibit DNA replication (2)
target ___
drug that inhibits mitosis (1)
target ___
drugs that inhibit hormone signaling (2)
targets __ and ___
drugs that inhibit cancer signaling/repair (4)
targets in order
bleomycin, cisplatin, cyclophosphamide
DNA
doxorubicin, etoposide
Topo2
paclitaxel
microtubules
anastrazole, tamoxifen
aromatase, ER
trastuzumab, bevacizumab, everolimus, olaparib
Her2neu, VEGF, mTOR, PARP
__ has more rapid MOA than ___
Cyclophosphamide __ CYP450
tamoxifen, anastrozole
activated by
