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17 Cards in this Set

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How do monoclonal antibodies differ from tyrosine kinase inhibitors in their sites of action (general)?
Monoclonal Ab's: act extracellularly

Tyrosine kinase inhibitors: small molecules that act intracellularly
Describe the ideal cancer target for a MAb.
Ideal target is:
-macromolecule crucial to malignant phenotype

-cell-surface Ag that upon binding a MAc will internalize by endocytosis and facilitate tumor cell killing

-Ag not expressed sig in vital organs and tissues

-Correlated w/clinical outcome
What does the FDA consider a targeted therapy?
Drug in which a specific diagnostic test must be performed in order for pt to be considered eligible for tx.
Imatinib:
Eligibility Criteria
Presence of Phil chromosome (BCR-ABL) gene to identify CML
Trastuzumab:
Eligibility Criteria
Overexpression of HER2/Neu protein or amplification of HER2 gene
Cetuximab:
Eligibility Criteria
EGFR overexpression
What are humanized MAb's? Advantages?
Humanized MAb's are developed in non-human species but with protein sequences modified to match those of humans.

Humanizing a MAb decreases immunogenicity, neutralizes Ab response and symptoms of allergy and anaphylaxis.
Rituximab:
MOA
Indication
Toxicities
-IgG kappa anti-CD20 Mab (only affects B cells! Only B cells have CD20!!)
Tox:
Infusion reaction (hypoxia, pulmonary infiltrates, MI, cardiogenic shock)
Tumor lysis syndrome

-B-cell Non-Hodgkin's Lymphoma

-Leads to apoptosis, Ab-dependent cell cytotoxicity, and complement-mediated cytotoxicity
What is radioimmunotherapy?
Strategy that optimizes efficacy of anti-CD20 MAb by cross-linking MAb to radioconjugate.

Radionucleotide enhances cytotoxicity of MAb against target cells and produces higher response rates than Rituximab.
Tositumomab:
MOA
Indication
Toxicities
Iodinated murine MAb against CD20

Indicated with relapsed or Rituximab refractory NHL

Tox:
Infusion reaction
Prolonged cytopenias
Mucocutaneous reactions
Ibritumomab:
MOA
Indications
Toxicities
Radioconjugated MAb for relapsed or Rituximab refractory NHL

Tox:
Infusion rxn
Prolonged cytopenia
Mucocutaneous rxns
Imatinib:
Drug Class
Indication
Tyrosine Kinase Inhibitor

Pts with Phil Chrom (BCR-ABL)--CML
Bevacizumab:
MOA
Toxicities
Binds VEGF and prevents interaction with receptors (dec'd endothelial cell prolif, dec'd BLOOD VESSEL formation!)

Tox:
GI Perforation
Poor wound healing
Bleeding
HTN
Cetuximab:
MOA
MAb that binds EGFR and prevents interaction with its receptors
Erlotinib:
MOA
Small molecule that inhibits phosphorylation of tyrosine kinases
Trastuzumab:
MOA
Toxicities
Binds to HER2 and prevents downstream signaling (dec'd cell growth/prolifern)

Tox: Cardiomyopathy (!), transfusion reaction
This drug can result in cardiomyopathy.
Trastuzumab