Term
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Definition
| work primarily in S phase, some G1. Generally inhibit multiple steps of DNA synthesis |
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Term
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Definition
| must be phosphorylated to be active. In the diphosphorylated form (gemcitabineDP) it inhibits ribonucleoside reductase. In the triphosphorylated form (gemcitabineTP) it inhibits DNA polymerase. Antimetabolites are not carcinogenic or leukemogenic |
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Term
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Definition
| work during S phase. These inhibit enzymes necessary for packaging/unpackaging DNA into chromosomes. |
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Term
| Topoisomerase I inhibitors |
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Definition
| probably do not kill cells by inhibiting topoisomerase (sounds weird but they kill cells at lower concentrations than are actually needed to inhibit enzymes,they do it by causing double stranded DNA breaks) TopoI is ATP independent and “less important” than TopoII. Examples are Irinotecan, topotecan, and campthecin. |
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Term
| Topoisomerase II inhibitors |
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Definition
| ATP dependent. Examples are etoposide, and anthracyclines (breaks DNA and can cause intercalations. |
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Term
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Definition
Doxorubicin is key example
Potential mechanisms of toxicity:
1. Stabilization of topoisomerase II-DNA adducts 2. Formation of free radicals
3. Intercalation
4. Inhibition of helicases
Specific Anthracycline toxicities:
1. Myelosuppression
2. Mucositis
3. Nausea/vomiting
4. CARDIAC TOXICITY -acute, cumulative, developmental
5. Radiation-sensitive dermatitis
6. Tissue necrosis at extravasation sites |
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Term
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Definition
| DNA Damaging (aka cross-linking) agents |
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Term
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Definition
| Antimitotics – bind tubulin and disrupt microtubules leading to failure of separation of daughter chromosomes at mitosis. |
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Term
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Definition
| Antibody to Her2, causes internalization and downregulaton |
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Term
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Definition
| monoclonal antibody to VEGF; anti-angiogenesis mechanism |
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Term
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Definition
| c-Kit inhibitor (an RTK, inhibiting these shuts down multiple signal transduction pathways that in general promote proliferation and anti-apoptosis) |
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Term
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Definition
| Inhibits dimerization of EGFR receptors (these are RTKs) |
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Term
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Definition
| Inhibits multiple kinases (Raf, VEGFR, PDGFRb, p38, c-Kit) |
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Term
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Definition
| binds to FKBP12 and inhibits mTOR |
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