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49 Cards in this Set

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What is tyrosine kinase?
Good question....
Enzyme (on cytoplasmic side) attached to transmembrane cell receptors (EGFR, VEGF, PDGFR) which, when activated, leads to phophorylation of proteins and ultimately cell proliferation

Sum: Ligand --> Receptor --> TK --> phosphorylation --> cell proliferation
What are EGFR & VEGF?
EGFR: epidermal growth factor receptor; linked to TK --> activation leads to cell proliferation
VEGF: vascular endothelial growth factor; angiogenic signaling (tumor recruits blood supply)
What is the role of inhibition of tyrosine kinase in cancer treatment?
(ex: cetuximab, trastuzumab)
Disrupt cell-signaling path (now the tumor cannot promote survival, proliferation, motility)
MOA: it binds receptor & prevents dimerization
What drugs are available that target EGFR?
EGFR:
small molecules: erlotinib gefitinib
monoclonal Abs: CETUXIMAB, panitumumab, TRASTUZUMAB (for Her2)
What drugs are available that target VEGF?
VEGF:
Bevacizumab,
probably others, but i don't care
What is Her2/neu?
In what cancers is it overexpressed?
1. Her2/neu: oncogene
2. overexpressed in breast cancers
What is the name of the monoclonal antibody against HER2?
Trastuzumab
Are methotrexate, 5-FU, Ara-C, and 6-MP CCS or CCNS?
CCS
What is the MOA of methotrexate?
inhibits dihydrofolate reductase which leads to a decrease in dTMP
What is the MOA of 5-FU?
converted to active --> 5-FdUMP --> inhibits thymidylatesynthase leading to a decrease in dTMP
What is the MOA of Ara-C?
inhibits DNA pol (or inhibits base stacking) leading to inability to elongate DNA
What is the MOA of 6-MP?
Activated by HGPRT
inhibits AMP/GMP synthesis!
What do you need to replenish when treating w/ methotrexate? What do you give to accomplish this?
Leucovorin --> replenishes folate
What are some AE's of methotrexate?
Reversible decrease in bone marrow
nephrotox --> give sodium bicarb
CNS tox
What is a MAJOR AE of 5-FU?
ischemia (to the heart)
In what cell cycle phase do methotrexate, 5-FU, Ara-C, and 6-MP act?
S phase
What are 2 major AE's of Ara-C?
Cerebellar toxicity
Ocular --> conjunctivitis, keratitis
(also myelosuppression)
What drug interacts w/ 6-MP by inhibiting its metabolism?
Allopurinol
(inhibits xanthine oxidase)
What are two common SE's of alkylating agents?
Bone marrow suppression
Alopecia
What is the MOA of busulfan?
Worst AE?
1. alkylates DNA via cross-linking
2. Pulmonary fibrosis
What is the MOA of cyclophosphamide?
attacksguanine N7 --> alkylates DNA
What is special about the nitrosureas? (lomustine, carmustine)
They cross the BBB!
What are the major AE's of cisplatin?
MOA-alkylates
AE: nephrotoxicity (hydrate w/ NS)
ototoxicity
neurotxic
N/V
What is the MOA of procarbazine?
methylates DNA
What is a common presentation of the major AE of doxorubicin?
CHF! (causes cardiomyopathy long-term)
(also see alopecia)
What is the MOA of doxorubicin?
inhibits topoisomerase II --> intercalates DNA --> breaks --> no replication/translation
What is the MOA of bleomycin?
makes free radicals--> damages DNA in G2 phase!
What is the major AE of bleomycin?
PULMONARY FIBROSIS

IN ALL CAPS
What 4 cancer types do you often use hormone/anti-hormone tx?
breast
prostate
endometrial
adrenal cortex
What type of cancer is aromatase-inhibitor used for?
breast cancer
What is the MOA of hydroxyurea?
inhibit ribonucleotide reductase --> dec dNTP (in S-phase)
What is the MOA of all-trans retinoic acid?
inhibits clonal proliferation (in acute promyelocytic leukemia)
What is the general MOA of the plant alkaloids group?
inhibit MT's in some way (usually affecting mitotic spindle formation)... so M phase
What is the MOA of vinblastine and vincristine?
inhibit MT
AE of cristine --> peripheral neuropathy
What is the MOA of docetaxel?
major AE?
stablize (and immobilize) MT's
AE: hypersensitivity reaction (must prophylax)
If a patient cannot make sufficient UGT-1A1, what drug should you avoid?
irinotecan
What is the MOA of etoposide?
inhibit topoisomerase II --> DNA degradation
This is the term for treating for micromets post surgery or radiation tx.
Adjuvant Chemotherapy
This is the term for treating (w/ chemo) prior to surgery (to shrink tumor).
Neoadjuvant chemotherapy
What is the MOA of mitomycin C?
alkylates DNA
for solid tumors
can cause bone marrow suppression
Pt. being treated w/ cisplatin may develop what major AE?
What is the treatment?
AE: nephrotoxicity
Tx: amifostine (forms thiol groups --> binds toxic metabolites)
What complication does Dexrazoxane address?
cardiotoxicity seen w/ doxorubicin
it is an iron chelator
What is the major AE of ifosphamide?
How would you treat this?
AE: hemorrhagic cystitis
Tx: Mesna (activate thiols --> bind toxicmetabolites)
What is the standard of care for treating chemo-induced N/V?
5-HT3-R antagonist
NK1-R antagonist
corticosteroid
What is the DOC for acute chemo-induced N/V?
5-HT3 receptor antagonists
(all end in -setron)
Pt. on chemo develops anemia. Treatment?
SE's?
1. ESA's (EPO-stimulating agent)
2. SE: death, DVT, tumor/disease progression (the usual)
Pt on chemo develops neutropenia
Treatment?
CSF's
Ex: filgrastim (G), Pegfilgrastim, Sargramostim(GM)
Pt. on chemo develops thrombocytopenia.
Treatment?
Opreleukin (IL-11)
Pt. on Busulfran develops hyperuricemia.
Treatment?
allopurinal (xanthine oxidase inhibitor)
or
Probenecid (blocks uric acid tubular reabsorption)