Cancer Drugs 1-3 Flashcards
(18 cards)
Methotrexate
DNA interferenceMechanism: blocks action of DFHR; looks like folate and acts as a “false substrate” fr DFHRDFHR (dihydro-folate reductase) = enzyme that reduces dihydrofolate (FH2) to tetrahydrofolate (FH4)FH2 Cradles activated methyl group, this activated methyl group is a substrate for MTX to be put onto the U to convert it to TMethotrexate is taken up and metabolized easily, especially by cancer cellsUses: in combination with C + 5-FU pretty effectively block the wheel from turning; can also used with leucovorin (mimics the substrate) to block up that arm of the reaction by putting too much!Used in Breast cancer, solid tumors
5-Fluoro-Uracil
DNA InterferenceMechanism: uracil is component of RNA; Thymidine is made from Uracine!** blocks DNA synthesis by preventing the addition of methyl group to convert uracil thymidineThymidylate synthase = enzyme that adds methyl group to uracil to make it thymidine; if you modify a uracil to have fluoro group on it, won’t be able to add the methyl group! (fluoro acts as enzyme inhibitor)** if you block the synthesis of T, you will pretty effectively block the proliferation of cellsUses: colorectal cancer; used orally
Doxorubin
Topoisomerase Intereference (Irinotecan)Mechanism: disrupts the operation of topoisomerase enzymesresults in DNA fragmentation and arrest of cellular developmentUses: treat solid tumors, especially breast and colon cancersSide Effects: common cytotoxic effects, and chronic use leads to defects of the cardiac muscle reduced contractility that results from such damage is dose-dependent and much more severe in women than in men
Cyclophosphamide
DNA cross-linkingMechanism: Two arms in the active drug that cross-link DNAComes as a prodrug that forms two active metabolites when degraded by humans** FIRST METABOLITE works by forming cross-linkages between and within DNA at guanine residuesprevents proper replication of DNAcell deathOrallyUses: hematologic cancers, breast cancer, Hodgkin’s Disease, leukemia, CMFSide Effects: in addition to the common cytotoxic effect listed above (especially leukopenia), also causes cystisis (bladder infection) via SECOND ACTIVE METABOLITE (acrolein)
Cisplatin
DNA cross-linkingMechanism: similar to CyclophosphamideIrreversible changes are made to the cellUses: solid tumors like breast cancerSide Effects: Similar to Cyclophosphamide, but also particularly nephrotoxic
Vincristidine
Microtubule interferenceMechanism: messing with the proper formation of spindles during cellular division; spindles are formed by the microtubules during separation of chromosomes in mitosis** Vincristidine INHIBITS microtubule formationUses: effective against solid tumors (esp breast) and hematologic cancersSide Effects: terrible nausea, diarrhea, etc.** Peripheral neuropathy can result after sustained use because long nerves use microtubules to transport critical compounds throughout the cell!
Paclitaxel
Microtubule interferenceMechanism: messing with the proper formation of spindles during cellular division; spindles are formed by the microtubules during separation of chromosomes in mitosisPaclitaxel ENHANCES it to the point that the spindles can’t be disassembled, which then kills the cellUses: effective against solid tumors (esp breast) and hematologic cancersSide Effects: terrible nausea, diarrhea, etc.** Peripheral neuropathy can result after sustained use because long nerves use microtubules to transport critical compounds throughout the cell!**
Bevacizumab
** Bev blocks VEGF – the idea is to cut off blood supply to the tumor and cause necrosisBUT VEGF is only one of many of these types of factors, so cut off blood supply to tumor and the other factors are up-regulated (so he says that it is not very effective!)** in fact, in breast cancer, Bev resulted in worse results and FDA pulled it from use hereUses: first in colorectal cancerSide Effects: Hypertension because endothelium needs continuous growth of vessels induced by VEGF to relieve the pressure on the older vessels, but if you are blocking VEGF, you won’t have these new vessels built and the pressure will increase (vasoconstriction)Also used to treat macular degeneration
Cetuximab
anti-EGFR antibody (receptor)Mechanism: EGFR monoclonal antibody treatment won’t work if there’s a KRAS mutationFOLFIRI (combination leucovoin + 5-FU + Irinotecan)Adding Cetuximab increases survival rates in pts w/o KRAS (wildtype)** Targeting the EGF Receptor on cell surface if there is a KRAS mutation, EGFR will be constitutively on, and no level of “breaking” will stop itUses: EGFR colorectal cancer, solid tumor therapiesSide Effects: GI and skin-related Epidermal growth factor: Itchy skin, acne, etc.
Transtuzumab
anti-HER2 antibody (receptor)Mechanism: HER2 is marker for poor prognosis in breast cancerHER2 is transmembrane receptor, overexpressed in breast cancerAdding Trastuzumab to best known drug therapy increased disease-free survival rates restored outcome of pt with HER2 mutation to that of a HER2-negative cancer (which typically has a much better prognosis)Uses: breast cancerSide Effects: cardiac because there are low levels of HER2 on cardiomyocytes, targeted in antibody treatment; therapy can lead to cardiac wasting and contractile dysfunction
Rituximab
antibody inhibitor (receptor)Mechanism: CHOP (standard tx) + Rit = significant increase in survival rateAnti-CD20 Ab that targets CD20 surface antigen on B-cell leukemiaUses: B-cell Leukemia
Gefitinib and Erlotinib
small molecule inhibitor (kinase inhibitor)Mechanism: targeted against EGFR, but also does affect other kinases** T790M = important because this mutation makes the cell resistant to EGFR-kinase inhibitors (especially Gefitinib)Use: Side Effects: skin toxicityIf you don’t have any skin toxicity, you don’t have any benefit from the drug (this is the way you know you have enough drug on board to make a difference)
Lapatinib
small molecule inhibitor (kinase inhibitor)Mechanism: targets HER2 (pretty specific – only targets HER2)Use:Side Effects: minimal because only targets HER2
Sorafenib and Sunitinib
small molecule inhibitor (kinase inhibitor)Mechanism: VEGF inhibitors, but very non-specific, result in widespread inhibition of kinases
Imatinib
small molecule inhibitor (kinase inhibitor)Mechanism: targets Abl in CML; collateral inhibition of unrelated kinasesIn CML, remember there is a translocation which results in the Philadelphia Chrom fusion protein (BCR-Abl) constitutive activation of Abl** Imatinib inhibits the abl kinaseCML can become resistant to Imatinib over time (then start using drugs that target further downstream targets)Use:Side Effects:
Vemurafenib
small molecule inhibitorMechanism: One of the mutations that can occur during course of tx is BRAF (we want to target this mutation!)reduction in tumor, but 100% recurrence rateCancer eventually becomes resistant to this tx as well* Targeting treatment DOES work, at least initiallyUses: metastatic melanomaSide Effects: squamous cell carcinoma (skin) Inhibition of RAF stops proliferation in melanocytes, but promotes proliferation in squamous cells Easier to cut out squamous cell carcinoma
Ipilimumab
1
Bortezomib
1
