Biochemistry of cancer

Biochemistry of cancer

1. Biochemistry of
CANCER
Dr.AzadAlamSiddiqui
Assistant Professor
Department of B.Voc(MMDT)
Km. Mayawati Govt.GirlsPG College
Badalpur, G.B. Nagar (U.P.)

2. Normal Cell
•Normalcellshavecertaincharacteristicsthatareimportantforthe
properfunctioningoftissues,organs,andbodysystems.
➢abilitytoreproducecorrectly,
➢stopreproducingwhennecessary,
➢remaininaspecificlocation,
➢specializedforspecificfunctions,
➢andselfdestructwhennecessary.
•CellReproduction:Cellreproductionisneededtoreplenishthecell
populationthatagesorbecomesdamagedordestroyed.Normalcells
reproduceproperly.Exceptforsexcells,allcellsofthebodyreproduceby
mitosis.Sexcellsreproducethroughaprocesscalledmeiosis.
•CellCommunication:Cellscommunicatewithothercellsthrough
chemicalsignals.Thesesignalshelpnormalcellstoknowwhento
reproduceandwhentostopreproducing.

3. •CellAdhesion:Cellshaveadhesionmoleculesontheirsurfacethatallow
themtosticktothecellmembranesofothercells.Thisadhesionhelps
cellstostayintheirproperlocationandalsoaidsinthepassageofsignals
betweencells.
•CellSpecialization:Normalcellshavetheabilitytodifferentiateor
developintospecialisedcells.Forexample,cellscandevelopintoheart
cells,braincells,lungcellsoranyothercellofaspecifictype.
•CellDeath:Normalcellshavetheabilitytoselfdestructwhenthey
becomedamagedordiseased.Theyundergoaprocesscalled
apoptosisinwhichcellsbreakdownandaredisposedofbywhiteblood
cells.

4. Cancer Cells
•Growth-cancercellsdon’tstopgrowingwhenthereareenoughcells
present.Thiscontinuedgrowthoftenresultsinatumor(aclusterof
cancercells).
•Communication-Normalcellsrespondtosignalssentfromother
nearbycellsthatsay,essentially,“you’vereachedyourboundary.”
Whennormalcells“hear”thesesignalstheystopgrowing.Cancercells
donotrespondtothesesignals.
•Cellrepairandcelldeath-Normalcellsareeitherrepairedordie
(undergoapoptosis)whentheyaredamagedorgetold.Cancercellsare
eithernotrepairedordonotundergoapoptosis.
•Stickiness—Cancercellsfailtosticktomembraneand“floataway”to
locationsnearby,orthroughthebloodstreamorsystemoflymph
channelstodistantregionsinthebody(Metastasis).

5. •Appearance—Underamicroscope,normalcellsandcancercellsmay
lookquitedifferent.somearelargerthannormalandsomearesmaller
thannormal.Inaddition,cancercellsoftenhaveanabnormalshape,
bothofthecell,andofthenucleus.
•Therateofgrowth—Normalcellsreproducethemselvesandthenstop
whenenoughcellsarepresent.Cancercellsreproducerapidlybeforethe
cellshavehadachancetomature.
•Maturation—Normalcellsmature.Cancercells,becausetheygrow
rapidlyanddividebeforecellsarefullymature,remainimmature.
Doctorsusethetermundifferentiatedtodescribeimmaturecells.
•Evadingtheimmunesystem—Whennormalcellsbecomedamaged,the
immunesystem(viacellscalledlymphocytes)identifiesandremoves
them.Cancercellsareabletoevade(trick)theimmunesystemlong
enoughtogrowintoatumorbyeitherbyescapingdetectionorby
secretingchemicalsthatinactivateimmunecellsthatcometothescene.

6. •Functioning—Normalcellsperformthefunctiontheyaremeantto
perform,whereascancercellsmaynotbefunctional.Forexample,
normalwhitebloodcellshelpfightoffinfections.
•Bloodsupply—Angiogenesisistheprocessbywhichcellsattractblood
vesselstogrowandfeedthetissue.Cancercellsundergoangiogenesis
evenwhengrowthisnotnecessary.
•Invasiveness—Normalcellslistentosignalsfromneighbouringcellsand
stopgrowingwhentheyencroachonnearbytissues(somethingcalled
contactinhibition.)Cancercellsignorethesecellsandinvadenearby
tissues.

7. •Thetermcancerappliestoagroupofdiseases
inwhichcellsgrowabnormallyandforma
malignanttumor.
•Malignantcellscaninvadenearbytissuesand
metastasize(establishsecondaryareasof
growth).
•Thisaberrantgrowthpatternresultsfrom
mutationsingenesthatregulateproliferation,
differentiation,andsurvivalofcellsina
multicellularorganism.
•Becauseofthesegeneticchanges,cancercells
nolongerrespondtothesignalsthatgovern
growthofnormalcells.

9. •Everysixthdeathintheworldisduetocancer,makingitthesecondleading
causeofdeath(secondonlytocardiovasculardiseases).
•In2016,8.9millionpeopleareestimatedtohavediedfromthevariousforms
ofcancer.
•AccordingtotheNationalCancerRegistryProgrammeoftheIndiaCouncilof
MedicalResearch(ICMR),morethan1300Indiansdieeverydaydueto
cancer.
•Between2012and2014,themortalityrateduetocancerincreasedby
approximately6%inIndia.
•BreastcancerandLungcancerkillthemostwomenandmenrespectively.
•Onewomandiesofcervicalcancerevery8minutesinIndia.
•Forevery2womennewlydiagnosedwithbreastcancer,onewomandiesofit
inIndia.
•Asmanyas2,500personsdieeverydayduetotobacco-relateddiseasesin
India.
•Smokingaccountsfor1in5deathsamongmenand1in20deathsamong
women,accountingforanestimated9,30,000deathsin2010.

10. The 10 Most Common Causes of Cancer Death: 2012 Estimates

13. •Neoplasmisanabnormalgrowthoftissuewhich,ifitformsamass,
iscommonlyreferredtoasatumor.
•Thetumorsareoftwotypes.
➢Benigntumors:Theyusuallygrowbyexpansionandremain
encapsulatedinalayerofconnectivetissue.Normallybenigntumors
arenotlife-threatening.eg.moles,warts.Thesetypesofbenign
tumorsarenotconsideredascancers.
➢Malignanttumorsorcancers:Theyarecharacterizedby
uncontrolledproliferationandspreadofcellstovariouspartsofthe
body,aprocessreferredtoasmetastasis.Malignanttumorsare
invariablylife-threatening.eg.Lungcancer/leukaemia
•Cancersarisingfromepithelialcellsarereferredtoascarcinomas
whilethatfromconnectivetissuesareknownassarcoma.

14. Etiology
•Cancersaremultifactorialinorigin.Thecausativeagentsinclude
physical,chemical,geneticandenvironmentalfactor.
•90%ofallcancerdeathsareduetoavoidablefactorssuchas
tobacco,pollution,occupation,alcoholanddiet.
•Mostofthecancersarecausedbychemicalcarcinogens,radiation
energyandviruses.TheseagentsmaydamageDNAorinterfere
withitsreplicationorrepair.
•Onemutationoccursoutof10
6
celldivisions.Bythetimeaperson
reachesadulthood,about10
26
celldivisionshaveoccurred.Thanks
tothesurveillancebytheimmunesystem,theseaberrantcellsare
usuallydestroyed.

15. Mutagens
•Substancethatincreasestherateofmutationalsoenhancetherate
ofincidenceofcancer.Therefore,allcarcinogensaremutagens.
•Somehumancancersarecausedbychemicals.(a)occupation(aniline,
asbestos),(b)diet(aflatoxins)or(c)lifestyle(smoking).
•Tobacco,foodadditives,colouringagents,andaflatoxinsarecommon
carcinogensinourenvironment.
•Chemicalcarcinogens:
•Almost80%ofthehumancancersarecausedbychemical
carcinogens:
1.Occupation.eg.Asbestos,benzene
2.Diet.eg.AflatoxinBproducedbyfungus(AspergiIIusfIavus)
contaminationoffoodstuffs,particularlypeanuts.
3.Drugs-certaintherapeuticdrugscanbecarcinogenic.eg.
diethylstibesterol.
4.Lifestyle.eg.Cigarettesmoking.

16. ➢Itisestimatedthatonecigarettereduces10minutesfromthe
lifespanoftheindividual.Theincidenceoflungcancerisincreasedto
15timesmoreinpersonssmoking10cigarettesperdayand40times
morewhensmoking20cigarettesperday.
➢non-smokingspouseofaheavysmokerwillhave5timesmore
probabilitytogetlungcancerthananon-smoker.

17. Mechanism of action
•Althoughafewofthechemicalsaredirectlycarcinogenicmajority
ofthemrequirepriormetabolismtobecomecarcinogenic.
•Achemicallynon-reactivepro-carcinogenisconvertedtoan
ultimatecarcinogenbyaseriesofreactions.
•Mostcarcinogensrequirepromotersfortheproductionofa
cancer.Benzo(a)pyreneappliedonskindoesnotproducecancer.
Crotonoilapplicationalsodoesnotleadtoskincancer.Butwhen
benzo(a)pyreneapplicationisfollowedbycrotonoil,tumoris
developed.Inthiscase,crotonoilistermedasthepromoter.
•2-acetylaminofluorene(AAF)wheningested,ismetabolizedto
producetheultimatecarcinogen,N-hydroxy-AAF.Theenzymes
responsiblefortheactivationofprocarcinogensarecytochromeP-
450system.

18. •Mechanisms of action of chemical carcinogens are:
a)Carcinogensaregenerallyelectrophilestheyreadilyattack
nucleophilicgroupsofDNA.
b)CarcinogensmaybindcovalentlytocellularDNA.N2,N3,andN7
atomsofguaninearehighlypronetoadditionofcarcinogen
groups.
c)ThesechangeswillleadtoDNAalterations,inspiteofDNA
repair,withincreasedprobabilityofmutations.
•Chemicalcarcinogensmayproducethecancer:
a)Atthesitofexposure,e.g.buccalcancerintobaccochewers,
skincancerintarworkers.
b)Atthesiteofmetabolism,e.g.livercancerproducedbyaflatoxin.
c)Atthesiteofelimination,e.g.bladdercancerinpersonsworking
witharomaticdyes.

19. Radiation energy
•X-ray,gamma-rayandUV-rayhavebeenprovedtobemutagenic
innatureandcausingcancerby:
1)formationofpyrimidinedimers,
2)apurinicsiteswithconsequentbreakinDNA,
3)formationoffreeradicalsandsuperoxideswhichcauseDNA
break,leadingtosomaticmutations.
ExposureofX-rayinfoetallifewillincreasetheriskofleukaemiain
childhood.Inpopulationstudies,1radiationperyearwillincrease
thecancerincidenceby40/millionpeopleperyear.

20. Ames assay:
•Atesttocheckthecarcinogenicityofchemicals.
•Amesassayemploystheuseofaspecialmutantstrainof
bacterium,namelySalmonellatyphimurium(His-).
•Thisorganismcannotsynthesizehistidine;hencethesameshould
besuppliedinthemediumforitsgrowth.
•Additionofchemicalcarcinogenscausesmutations(reverse
mutation)restoringtheabilityofthebacteriatosynthesize
histidine(His+).
•BydetectingthestrainofSalmonella(His+)inthecoloniesofagar
plates,thechemicalmutagenscanbeidentified.
•TheAmesassaycandetectabout90%ofthechemical
carcinogens.Thistestisregardedasapreliminaryscreening
procedure.Animalexperimentsareconductedforthefinal
assessmentofcarcinogenicity.

21. Thesearesubstanceswhichwillinterferewithtumorpromotion.
1)VitaminAandcarotenoidsareshowntoreverseprecancerous
conditions.
2)VitaminEactsasanantioxidant,preventingthedamagemadebyfree
radicalsandsuperoxides.
3)VitaminCregularlygiventopersonsworkingwithanilineprevented
theproductionofnewcancercases.
4)Tubers,beansandleafyvegetablesareshowntointerrupttumor
promotion.
5)Curcumin,theyellowsubstanceinTurmericisknowntoprevent
mutations.
6)Lowprotein,lowfat,dietdecreasestheriskofcancerinanimal
studies.
7)Phenoliccompoundsfoundinfruitslikegrapes,strawberries,walnuts,
etc.arefoundtobeantimutagenic.Greenteaisshowntobeeffective
againstsmokeinducedmutations.
Antimutagens

22. Carcinogenic viruses
•TheinvolvementofvirusesincancerwasfirstreportedbyRousin
1911.
•cell-freefiltratesfromcertainchickensarcomas(tumorsof
connectivetissues)promotenewsarcomasinchickens.
•ButthisimportantdiscoveryofRouswasignoredforseveralyears.
•RouswasawardedtheNobelPrizein1966attheageof85forhis
discoveryin1911.
•DNAofMalignantcellsshowspresenceofviralparticlesandthe
enzymereversetranscriptasebesidestheoccurrenceofbase
sequence.
•Thevirusesinvolvedinthedevelopmentofcancer,commonly
knownasoncogenicviruses.
•OncogenicvirusesmaybeeitherDNAvirusesorRNAviruses.

23. ➢Burkittin1964reportedatypeoflymphomaseenmainlyin
Africanchildren.
➢In1969,EpsteinreportedthatallthebiopsiesofBLwhenplaced
intissuecultureforsometime,generatedtheviralparticles
whichcouldbeseenunderelectronmicroscope(Barrwasthe
technicianwhofirstperfectedthistechnique).Thenewviruswas
namedasEpstein-Barr(EB)virus.

24. ▪Oncogenes–Thegenescapableofcausingcancerareknownas
oncogenes.Oncogeneswereoriginallydiscoveredintumor
causingviruses.
▪Proto-oncogenes–Proto-oncogenesareagroupofgenesthat
causenormalcellstobecomecancerouswhentheyaremutated.
Mutationsinproto-oncogenesaretypicallydominantinnature,
andthemutatedversionofaproto-oncogeneiscalledan
oncogene.
▪Tumorsuppressorgenes-(normalgrowthsuppressor
genes)--encodeproteinsthatinhibitproliferation,promotecell
death,orrepairDNA
Activation of oncogenes or absence /inactivation
of tumor suppressor genes can lead to cancer.

25. DNA VIRUSES
•ThreeDNAviruseshavebeenestablishedascausinghuman
cancers,viz.EBV,HBVandHPV:
a)Burkitt’sLymphoma:
•BelongstoherpesfamilyandproducesBurkitt’slymphoma.
•ItisatumorofBlymphocytesthatisconsistentlyassociatedwitha
[t8:14]translocation.
•ItisendemicinAfricaandpatient’stumorcellscarryEBVgenome.
•EBValonecannotcausethetumor.EBVcausessustainedB-cells
proliferation;theyacquireadditionalmutationsandsometimes
translocation[t8:14]andbecomestumorigenic.
b)HepatitisBVirus(HBV):
•HepatitisBvirusinfectionisfoundtobecloselyassociatedwith
formationoflivercancer.

26. c) Nasopharyngeal Carcinoma :
•Is endemic in southern China.
•EBV genome is found in all such tumour cells.
d) Human Papillomavirus (HPV):
•isthemostcommonsexuallytransmittedinfectioninadults.
•HPVtypes16and18areassociatedwithhumanuterinecervical
cancer;theycause70%ofallcervicalcancers.
•HPVinfectsepithelialcellsinthecervicalmucosa;thevirus
multipliesandlysesthehostcells,causingalesion.
•In99%ofsuchcaseshealingoccurswithin6monthsto2years.But
inabout1%cases,theHPVDNAisintegratedintosomeofthehost
cellsanddevelopinvasivecancer.
•VaccinesagainsthighriskHPV16and18typesarenowdeveloped
thatprovide95%protectionfrominfectionofHPV,thereby
reducingthechancesofdevelopingcervicalcancer.

27. RNA VIRUSES
•All oncogenic RNA viruses are retroviruses
Human T-Cell Leukaemia Virus (HTLV):
•HTLV-1,foundassociatedwithhumanleukaemia/lymphoma.
•ItisendemicinpartsofJapan.Sporadiccasesseeninotherparts.
•HTLV-1containsasegmentinitsgenomecalled“tat”.Theproteins
encodedby‘tat’genearebelievedtoberesponsiblefor
transformation.
•Theyaffectthetranscriptionofcertaingrowthfactorsand
receptorslikeIL-2andIL-2R.

28. •Inchronicmyeloidleukaemia,
deletionofshortarmof
chromosome 22, called
Philadelphia(Ph’)chromosomeis
seenin80%cases.Intherest,
thereistranslocationof9to22
leadingtoactivationofc-abl
presentinchromosome9.
•Innon-Hodgkin’slymphoma,
translocationofchromosome14to18
isverycommon,involvingthebcl-2
oncogene.Thebcl-2product
suppressesprogramedcelldeath
leadingtotumorformation.

29. Activation of proto-oncogenes to oncogenes
1.Viral insertion into chromosome:

30. 2.Chromosomaltranslocation:Someofthetumorsexhibit
chromosomalabnormalities.Thisisduetotherearrangementof
geneticmaterial(DNA)bychromosomaltranslocationi.e.splitting
offasmallfragmentofchromosomewhichisjoinedtoanother
chromosome.Chromosomaltranslocationusuallyresultsin
overexpressionofproto-oncogenes.
Burkitt'slymphoma,a
cancerofhumanB-
lymphocytes,isagood
exampleofchromosomal
translocation.Inthiscase,a
fragmentfromchromosome
8issplitoffandjoinedto
chromosome14.

31. 3.Geneamplification:SeveralfoldamplificationsofcertainDNA
sequencesareobservedinsomecancers.Administrationof
anticancerdrugsmethotrexate(aninhibitoroftheenzyme
Dihydrofolatereductase)isassociatedwithgeneamplification.The
drugbecomesinactiveduetogeneamplificationresultingina
severalfold(about400)increaseintheactivityofdihydrofolate
reductase.

32. 4.Pointmutation:Therasproto-oncogeneisthebestexampleof
activationbypointmutation(changeinasinglebaseintheDNA).
Themutatedrasoncogeneproducesaprotein(GTPase)which
differsinstructurebyasingleaminoacid.Thisalterationdiminishes
theactivityofGTPase,akeyenzymeinvolvedinthecontrolofcell
growth.
•Thepresenceofrasmutationsis
detectedinseveralhuman
tumors-90%ofpancreatic,50%
ofcolonand30%oflung.

33. Some cellular oncogenes

34. Mechanism of action of oncogenes
•Oncogenesencodeforcertainproteins,namelyoncoproteins.
•Theseproteinsarethealteredversionsoftheirnormal
counterpartsandareinvolvedinthetransformationand
multiplicationofcells.
•Growth factors :
•Severalgrowthfactorsstimulatingtheproliferationofnormalcells
areknown.Theyregulatecelldivisionbytransmittingthemessage
acrosstheplasmamembranetotheinteriorofthecell
(transmembranesignaltransduction).ltisbelievedthatgrowth
factorsplayakeyroleincarcinogenesis.

35. •Thecellproliferationisstimulatedbygrowthfactors.
•Agrowthfactorbindstoaproteinreceptorontheplasma
membrane.
•Thisbindingactivatescytoplasmicproteinkinasesleadingtothe
phosphorylationofintracellulartargetproteins.
•Thephosphorylatedproteins,inturn,actasintracellular
messengerstostimulatecelldivision.
•eg.Transforminggrowthfactor(TGF-α)isaproteinsynthesized
andrequiredforthegrowthofepithelialcells.TGF-αisproduced
inhighconcentrationinindividualssufferingfrompsoriasis,a
diseasecharacterizedbyexcessiveproliferationofepidermalcells.
How Growth Factors Work

37. Differences between Normal and Tumor
cells Tumor Kinetics
•ThecellcycleisdividedintoG1,S,G2andMphasesand
completeswithin18–24hours.Thecellcycletimeismoreorless
samefornormalcellsandcancercells.
•Inanormaltissue,only1%cellsareinthedividingstate.In
cancertissues,about2–5%ofcellsareinthecellcycleandthis
numberdemarcatesamildlygrowingtumor(2%)froman
aggressiveone(5%).
•Thisdifferenceisusedforthetreatment.Cytotoxicdrugsand
radiationwillkillthecellsinthecellcycle,whilesparingthe
restingcells.Cyclindependentkinaseinhibitors(p16andp27)
havebeenshowntobelostinvariouscancers.

38. Doubling Time
•Thedoublingtimeisthetimetakenbyatumortoexactly
doubleitsmass,andisaconstantforaparticulargrowthovera
longperiod.
•Thetumordoublingtimeinhumancancersvarieswidely
between10daysto450days,withameanofabout100days.
•Veryrapidlygrowingtumorswillneedlesserdaystodoublethe
volume.
•Inthecaseoftumorwithadoublingtimeof100days,thetime
takenforthisgrowthtoreach1cmsizefromtheinitialmutated
cellisabout8–10years.
•Thus,thetumorwaspresentinthebodyforaconsiderable
periodbeforetheclinicaldetection.
•Thesamefactexplainsthedevelopmentofthesecondaries
severalyearsafterthetreatmentoftheprimarygrowth.

39. •GTP-bindingproteins:
•Theseareagroupofsignaltransducingproteins.Guanosine
triphosphate(GTP)-bindingproteinsarefoundinabout30%of
humancancers.
•Themutationofrasproto-oncogeneisthesingle-mostdominant
causeofmanyhumantumors.
•TheinactiverasisinaboundstatewithGDP.Whenthecellsare
stimulatedbygrowthfactors,rasP21getsactivatedbyexchanging
GDPforGTP.
•Thisexchangeprocessiscatalysedbyguaninenucleotidereleasing
factor(GRF).
•TheactiverasP21stimulatesregulatorssuchascytoplasmic
kinases,ultimatelycausingDNAreplicationandcelldivision.
•Innormalcells,theactivityofrasP21isshortlived.TheGTPase
activity,whichisanintegralpart(intrinsic)ofrasP21,hydrolyses
GTPtoGDP,revertingras21totheoriginalstate.

40. Anti-oncogenes or cancer-suppressor Genes
•Thegenes,whichnormally
protecttheindividualfrom
gettingthecancer.
•RBgeneencodesaprotein
(p105)thatsuppresscell
proliferation,andprevent
theactivityofvarious
oncogenes.
•Retinoblastomaoccurs
onlywhenbothallelesof
theRBgenearedeleted.

41. Role of p53
•Apartofshortarmofchromosome17wasshowntobedeletedin
varioushumancancers.Thisregionisnowknowntocontainan
onco-suppressorgene,calledp53.
•Thisgeneencodesaphosphoproteinwithmolecularweight
53kDa.
•ItblocksthecellsthathavedamagedDNAbytriggeringthe
productionofanotherproteinp21,whichblockscelldivisionuntil
thedamageisrepaired.
•IftheDNAdamageissevere,p53directsthecelltocommitsuicide
byapoptosis.
•Mosttumorshaveacompleteabsenceofp53,whereasothers
showmutantnon-functionalp53.
•Itisalsoseenthatp53activatestheexpressionofgenesthat
suppresscellproliferation.

42. Tumor Immunology
•Allformsoftreatmentofcancer(surgery,radiotherapyand
chemotherapy)leavesomeresidualcancercellsinthebody.
Theseareannihilatedbythebody’simmunemechanism.
•(a)Tcells,(b)NKcells,(c)antibodydependentcomplement
mediatedlysis,(d)antibodydependentcellmediatedcytolysis
(ADCC),and(e)macrophagesplayroleinremovalofthesecancer
cells.
•Inthetumorbearinghost,appreciablelevelofimmunological
reactionagainstthecancerisdetected.Thisisbecauseofthe
presenceoftumorassociatedantigens(TAA)onthesurfaceof
cancercells.

43. TUMOR MARKERS
•Thebiochemicalindicatorsthatdetectthepresenceofcancers
arecollectivelyreferredtoastumormarkers.
•Thesearetheabnormallyproducedmoleculesoftumorcells
suchassurfaceantigens,cytoplasmicproteins,enzymesand
hormones.
•Theyareusefulforthefollowingpurposes:
1.Forfollow-upofcancerandtomonitortheeffectivenessofthe
therapyandalsotodetecttherecurrenceofthetumor.
2.Tofacilitatedetectionofcancer.Thepresenceoftumormarker
suggeststhediagnosis.
3.Forprognosis.Serumlevelofthemarkermayindicateroughly
thetumorload,whichinturnindicateswhetherthediseaseis
curableornot.

44. Clinically Important Tumor Markers
•Alpha Fetoprotein (AFP):
•Itisfetalalbuminandhassimilaritieswithadultalbumin.
•Itisincreasedinthecirculationofpatientswithhepatocellular
carcinoma,germcelltumors,teratocarcinomaofovaryandin
pregnancywithfetalmalformationsofneuraltube.
•Inadultmalesandnon-pregnantfemales,normalvalueislessthan
15ng/L.AvalueofAFPabove300ng/Lisoftenassociatedwith
cancer(althoughlevelsinthisrangemaybeseeninnon-malignant
liverdiseases).
•Levelsabove1000ng/Larealmostalwaysassociatedwithcancer
(exceptinpregnancy).
•ThefucosylatedfractionofAFP(AFP-L3)hasbeenreportedtobea
morespecificmarkerforhepatocellularcarcinoma.

45. •Carcinoembryonic Antigen (CEA):
•Thisisacomplexglycoprotein,normallyproducedbythe
embryonictissueofliver,gutandpancreas.
•TheCEAlevelismarkedlyincreasedincolorectalcancers.
•Over50%ofpersonswithbreast,colon,lung,gastric,ovarian,
pancreatic,anduterinecancerhaveelevatedlevelsofCEA.
•CEAlevelsmayalsobeelevatedininflammatoryboweldisease
(IBD),pancreatitis,andliverdisease.Heavysmokersandabout
5%ofhealthypersonshaveelevatedplasmalevelsofCEA.
•Duetothis,CEAlacksspecificityforcancerdetection.

46. Beta Chain of Chorionic Gonadotropin:
•Beta-hCGissynthesizedbynormalsyncytiotrophoblasts(cells
ofplacentalvilli).
•hCGisaglycoprotein;ithasalphaandbetasubunits.Thealpha
subunitisidenticalwiththoseofFSH,TSHandLH.
•ThebetasubunitisspecificforhCG.Itisincreasedin
hydatidiformmole,choriocarcinomaandgermcelltumors.
About60%oftesticularcancerssecretehCG.
•Normalvalueislessthan20IU/Lformalesandnon-pregnant
females.Greaterthan100,00IU/Lindicatestrophoblastic
tumor.

47. Cancer Antigen 125
•CA-125isatumormarkerforovariancancers.Itisaglycoprotein
withamolecularweightof10million.
•Approximately75%ofpersonswithovariancancerwillhave
elevatedserumlevels.
•ElevatedlevelsofCA-125arealsofoundinapproximately20%of
personswithpancreaticanddigestivetractcancers.
•Thistestisusedtodeterminewhetherrecurrenceofthecancer
hasoccurredfollowingchemotherapy.
•NormalbloodlevelofCA-125islessthan35U/mL.

48. Common tumor markers

49. Cancer therapy
•Chemotherapy,employingcertainanticancerdrugs,iswidelyused
inthetreatmentofcancer.
•Theeffectivenessofcytotoxicdrugsisdirectlyproportionaltothe
doublingtimeofthetumors.
•Theeffectivenessofanticancerdrugsisinverselyproportionalto
thesizeofthetumor.
•Themajorlimitationofcancerchemotherapyisthattherapidly
dividingnormalcells(ofhematopoieticsystem,gastrointestinal
tract,hairfollicles)arealsoaffected.
•Celldestructionbycytotoxicdrugfollowsthefirstorderkinetics,
thatis,itreducesaconstantpercentageandnotaconstant
numberofcancercells.

50. Common Anti-Cancer Drugs

51. ➢Methotrexate:
•Itinhibitsdihydrofolatereductase.
•Inpresenceofmethotrexate,tetrahydrofolicacidisnot
produced,whichisnecessaryforincorporationofC2andC8of
purinesandC5methylgroupinthymidine.
➢6-Mercaptopurine:
•ItpreventsaminationofIMPtoAMP,sothattheavailabilityof
AMPisreduced.ThisleadstoinhibitionofsynthesisofDNA,
andinturncelldivision.
➢5-Fluorouracil:
•Fluorouracilwillinhibitthymidylatesynthase,therebyreducing
theconversionofdUMPtodTMP.
•TherebythymineincorporationintheDNA,andconsequent
DNAsynthesisareprevented.

52. ➢Cyclophosphamide:
•Itisextensivelyusedindifferentcancers,especiallylymphomasand
myeloidleukaemia.
•Itisanalkylatingagent,causingcrosslinkagebetweenadjacentbasesof
thedoublehelix.
•DNAstrandscannotseparate,andnewDNAsynthesisisblocked.
➢MitomycinC:
•ItisderivedfromStreptomyces.Thedrugcausescrossbridgebetween
DNAstrands,preventingseparationofstrands,andinhibitingnewDNA
synthesis.
➢VincristineandVinblastine:
•Theyarealkaloidsisolatedfromtheleavesofperiwinkleorvincarosea.
•In1958,IrvingJohnsonfirstestablishedtheclinicalusefulnessofthedrug
inhumanleukaemia's.
•Thedrugsarenowwidelyusedinleukaemia's,lymphomasaswellasin
solidtumors.
•cellsarearrestedinmetaphaseandcelldivisionisinhibited.

53. Monoclonal Antibody
•Thesedrugsarearelativelynewinnovationincancertreatment.
1.Theantibodymarksthecancercellandmakesiteasierforthe
immunesystemtoattack.
•ThedrugrituximabattachestoCD20foundonlyonBcells;
makesthecellsmorevisibletotheimmunesystem,whichcan
thenattack.
2.Blockgrowthfactors:
•Certaincancercellsmakeextracopiesofthegrowthfactor
receptor.Thismakesthemgrowfasterthanthenormalcells.
Monoclonalantibodiescanblockthesereceptorsandprevent
thegrowthsignal.
3.Stopnewbloodvesselsfromforming:
•MonoclonalantibodiesblocksgrowthSignalsfromcancercells
thatmayhelppreventatumorfromdevelopingabloodsupply.

54. Prevention of Cancer
•certainprecautionarymeasuresareadvocatedtopreventor
reducetheoccurrenceofcancer.
•Mostimportantamongthem,fromthebiochemicalperspective,
aretheantioxidantsnamelyvitaminE,β-carotene,vitaminCand
selenium.
•Theantioxidantspreventtheformationordetoxifytheexistingfree
radicals.Inaddition,antioxidantsstimulatebody'simmunesystem,
andpromotedetoxificationofvariouscarcinogens.
•most of the vegetables and fruits are rich in antioxidants. Their
increased consumption is advocated to prevent cancer.