Own Notes-Anticancer 2

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  • 7/24/2019 Own Notes-Anticancer 2

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    Anticancer Drugs 2 Novel anticancer agents

    Monoclonal antibodies Biological response modifiers Cytokine treatment Protein-kinase inhibitors Sensitising agent

    METHOD

    1) Immunize mouse to obtainantibodies2) Isolate antibody-formingcells from spleen3) Fuse these cells withtumour cells to formhybridomas4) Hybridomas screening for

    antibody production) !ntibody-producinghybridomas cloned") !ntibiodies isolated forculti#ation

    $ptional% !ttach cytoto&icagent to cloned antibody

    Immune system cannot 'byitself) detect and remo#e cancercells(

    esired action is to remo#eimmune cells and modify themto detect cancer(

    imitation!*imited cancers

    +rocess 'interleu,in-2)1) emo#e patient.slymphocytes and growin culture2) /ensitise themagainst tumour cellantigens

    'culture0antigen0I*2)3) einect these cellsthat are moreaggressi#e againsttumour

    1) small molecule. drugs bindto enzyme.s !+ binding site2) Inacti#ate the enzyme3) /ome may wor, to inhibitangiogenesis as well(

    esult isrupt signallingprocess halts cell di#ision

    and proliferation

    imitation! *imited cancers'leu,aemia 5I tumours) 6cell may proliferate #ia othersignalling molecules'as protein cd,s)

    Urinary bladder tumour

    - 785 used to immuniseagainst 7 but 785 canalso be used to ma,e cellsmore immunoreacti#e(- Induces inflammatoryaction increasesli,elihood cancer cells are

    attac,ed by immune cells

    '8ancer cells ta,e up785 immune system canidentify cancer cells)

    D"#$S

    "%ti&imabirected towards 829surface antigen o#ere&pressedon 7 cells in non-Hodg,in.slymphoma triggering 7-celllysis

    Trast%'%mab (Herceptin)7inds to human epidermalgrowth factor 2 'H:2) whichis o#ere&pressed in somebreast cancer forms(

    *nterferons- !ugments the cytoto&icity ofimmune cells- High doses inhibit cellproliferation facilitatecytoto&icity- !lter antigen e&pression ontumour cells and immune cells

    *nterle%kin-+ (*+)/timulates lymphocyteproliferation andcellular immunity;or,s on #arious cells7

    Tyrosine ,inase!asatinib lapatinib etc(

    Serine-threonine kinaseinhibitor!7-raf proto-oncogenesereine>threonine protein,inase '7!F)

    Treatment Complications Managing d.erse Dr%g "eactions

    Dr%g resistance T%mo%r cell sanct%aries Dose e&ha%stion ntiemetic dr%gs (Pre.ent na%sea/.omiting)opamine serotonin '#ia 5I) neuro,inin receptor antagonists

    '+re#ent triggering of #omiting sensation in medulla of brain)?a&alon 'cheaper first option) $ndensetron 'e&pensi#e)((e&amethasone @ ! glucocorticoid longer acting thanprednisolone that has antiinflammatory effects in 5I decreasingemetic stimuli to brain

    Colony Stim%lating 0actors (CS0s)Filigrastim 'Increase ;78):rythropoietin 'Increase 78)

    Organ to&icity?esna% Ased in conuction with cyclophosphamide and ifosfamide

    8omplication /pontaneous rapid

    mutations allow cancer cellto acBuire adaptations thatprotects it

    umour cells grow in

    compartments that areinaccessible to drugscreating sites of relapse

    ?a&imum therapeutic

    dose and immuneresponse of patientnot enough to attac,remaining cellsC anyincrease is to&ic

    /trategies 1) ?ultiple cytoto&ic drugtherapy @ ?ultiple drugswith differing actions2) rug holiday% !ttac, atdifferent times whendifferent cells are at cell

    adiotherapy andsurgery on top of drugs:(g( brain due toblood-brain barrier

    ?ultiple drug therapyradiotherapy surgeryand chemotherapycombinations

  • 7/24/2019 Own Notes-Anticancer 2

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    Anticancer Drugs 2 Novel anticancer agents

    cycle desired to pre#ent bleeding in urinary bladder