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28 Cards in this Set
- Front
- Back
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most common "off target" side effects
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cardiovascular and endocrine
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mAb targeting VEGF receptor
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bevacizumab
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mAb targeting EGF receptor
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cetuximab, panitumumab
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mAb targeting CD20 receptor
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rituximab, ofatumumab
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mAb targeting HER2 receptor
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trastuzumab
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mAb targeting CTLA-4 receptor
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ipilimumab
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target of Bortezomib
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26-S proteasome (inhibitor)
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mechanism of action of Trastuzumab
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Binds to the HER2 receptor to immediately inhibit signaling.
HER2 receptor is downregulated, CDKI p27 accumulates and causes cell cycle arrest. |
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mechanism of action of Pertuzumab
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Blocks HER2 and HER3 interaction - HER2 cannot phosphorylate HER3's cytoplasmic domain, no promotion of PI3 kinase cascade
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mechanism of action of Cetuximab and Panitumumab
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Binds to the EGF receptor to immediately inhibit receptor signaling
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mechanism of action of T-DM1
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mAb conjugated to the cytotoxic agent DM1 that binds to HER2 to prevent signaling while simultaneously delivering the cytotoxic agent
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mechanism of action of Ipilimumab
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Immunostimulant - binds to the CTLA-4 receptor on T cells to prevent binding of CD80/86 and increase activation and proliferation.
Increases T-cell mediated antitumor immune response. |
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mechanism of action of Rituximab
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Binds to the CD20 transmembrane protein on B cell precursors and mature B cells, which regulated an early step in activation - rapid and sustained depletion of B cells.
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activation of VEGF receptor
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When oxygen is low, hypoxia inducible factor (HIF-1) no longer degraded by 26S proteasome complex - instead translocates to nucleus to increase expression of VEGF receptor
Promotes angiogenesis and increases tumor survival. |
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Typical adverse effects of mAbs
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infusion related reaction - anaphylaxis, angioedema, pulmonary toxicity
left ventricular dysfunction, CHF, HTN depletion of cell populations in blood when target is expressed in that cell |
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consequences of antibody-epitope binding
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ADCC & CDCC
promotion of apoptosis direct delivery of drug blockage of receptors ligand blockage receptor down-regulation |
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mechanism and toxicity of Trastuzumab
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apoptosis and ADCC via EGFR-2 and HER-2 receptors
cardiomyopathy, infusion reaction |
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mechanism and toxicity of Cetuximab
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apoptosis and ADCC via EGFR-1 & HER-2 receptors
infusion reaction, skin rash with sun |
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mechanism and toxicity Panitumumab
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apoptosis and ADCC via EGFR-1 & HER-1
infusion reaction, skin rash with sun |
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mechanism and toxicity Bevacizumab
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anti-angiogenesis and neovascularization via VEGFR block
HTN, CHF, pulmonary hemorrhage, GI perforation |
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mechanism and toxicity Rituximab
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apoptosis, ADCC, & CDC via CD-20
infusion reaction, B-cell depletion, lymphopenia |
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Ofatumumab
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apoptosis, ADCC, & CDC via CD-20
infusion reaction, infections, progressive leukoencephalopathy, neutropenia |
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side effects of TKIs
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abnormal thyroid function, decreased bone density, abnormal PTH and vit D levels
Can affect pubertal and fetal development |
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TKIs causing cardiovascular and hepatic dysfunction
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Lapatinib and Nilotinib
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mechanisms of resistance to TKIs
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decreased intracellular drug levels, increased plasma protein binding, MDR-1 (p-gp) mediated efflux, genomic amplification of kinase, clonal evolution of kinase-independent mechanism, mutations of ATP-binding site
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inhibitors of mTOR
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sirolimus, everolimus, and temsirolimus via interaction with FK BP-12
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consequences of proteasome inhibition by Bortezomib
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IkappaB - NFkappaB inhibited for apoptosis, growth inhibition, & reduced angiogenesis
CDKs - G1-S cell cycle arrest & apoptosis P53 - apoptosis via p21 upregulation and Bax overexpression Bax - overcomes Bcl-2 overexpression to cause apoptosis Cyclins - apoptosis Damaged cellular proteins - accumulation leads to apoptosis |
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adverse effects of Bortezomib
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hypotension (additive), cardiotoxicity (acute onset CHF, QT prolongation), severe sensory and motor peripheral neuropathy, hematologic toxicity, hepatotoxicity, pregnancy risk cat. D
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