RESEARCHROUND-UP
AACRAdvancesinOvarianCancerResearch–ExploitingVulnerabilities
By:LauraKoontz,PhD
Earlierthismonth,weattendedtheAACRconferenceAdvancesinOvarianCancerResearch:Exploiting
Vulnerabilities,whichhighlightedmanyrecentpre-clinicaladvancementsinthetreatmentofovarian
cancer.Muchoftheworkpresentedwashotoffthepressesandunpublished–sowewereaskednotto
sharetoomanydetailsfromtheworkpublicly.Torespectthemeetingorganizers’wishes,wewillonly
generallysummarizesomeoftheadvancesdiscussedbelow.
Severalkeyareasofworkwerediscussedthroughouttheconference:(1)ovariancancerscreening(2)
targetingDNArepairpathwaysasawaytotreatovariancancer;(3)immunotherapy;and(4)advancesin
thetreatmentofraretumortypes.Finally,theconferencealsofeaturedapaneldiscussionwithpatient
advocates–includingOCNA’sBoardPresident,DianeRaderO’Connor,andSTSPresenter,CarlaJimenez.
OvarianCancerScreening
KeynotespeakerDr.UshaMenondescribedhernearlytwodecadesofworkontheUnitedKingdom
CollaborativeTrialofOvarianCancerScreening(UKCTOCS),whichisexpectedtobecompletelaterthis
year.Inshort,theUKCTOCSstudyexamineswhetherwomenwithanaverageriskofovariancancerwill
benefitfromhavingannualCA-125tests.Inthetrial,womenhadanannualCA-125andthenlooked
yearafteryearatthechangeinCA-125number,incombinationwithariskalgorithmcalledROCA.
Preliminaryresultshavesuggestedthatthisapproachmaybeusefulincatchingovariancancerinan
earlierstage(2or3,vs.3or4),butitisnotyetknownifthisactuallyequateswithwomenlivinglonger
lives.ThefullresultsofthetrialwillbeavailableonDecember17,2015,sostaytuned!
ExploitingtheDNARepairPathwayintheTreatmentofOvarianCancer
Manyovariancancertumorsresultfromproblemswithacell’sabilitytorepairdamagetoitsDNA–the
geneticblueprint.Assuch,thesecellsaccumulatealotofmutationswhichallowthemtogrowand
dividerapidly,resultingincancer.However,thestrengthofthesecellsmayalsobetheirgreatest
weakness–inrecentyears,researchershavebeenlearninghowtoexploittheovariancancercell’sDNA
repairproblemstotargetandkillthem.
ThefirstsuchadvancementinthisareawasthedevelopmentofPARPinhibitors,anewclassofdrugfor
ovariancancer,whichexploitsacell’sabilitytorepairitsDNA.Recently,someresearchershave
speculatedthatcombiningPARPinhibitorswithotherdrugsthatalsoexploitthisvulnerabilitymight
havesynergisticeffectsandbeanevenbettertherapyforovariancancer.Atthemeeting,researchers
presentedworkexaminingmanyothertargetsthatcouldbeusedwithPARPinhibitors,includingCDK,
PI3K,ATR,Chk1,andUSP11.Iftheywork,thesecombinationsofdrugscouldbeexpandtheuseofPARP
inhibitorsbeyondwomenwithBRCAmutations.Sufficetosay,it’sanexcitingtimewithlotsofpotential.
Immunotherapy
Researchersalsospentquiteabitoftimediscussingnovelideasinimmunotherapyforovariancancer.
Asyoumayknow,immunotherapyworksbyharnessinganindividual’sinnateimmunesysteminthe
fightagainsttumorcells.Therearetwomajortypesofimmunotherapy–thosewhichusedrugstohelp
activatetheimmunesystem,andthosewhichusesuperversionsofaperson’sownimmunesystemcells
tofightoffcancer.Muchofthepresentationatthismeetingfocusedonthelatter.Althoughtherehave
beenafewtrialsusinginnateimmunotherapyinthetreatmentofovariancancer,thefieldisstillina
relativelyearlystage.Manyoftheresearchersattheconferencepresentedpreliminaryresearchthat
willlaythegroundworkforfuturetrialsinovariancancer,includinginvestigatinghowtopickwhich
patientsmightbenefitthemostfromimmunotherapyandnewtypesoftherapy.
Rarecancers
TheAACRconferencewasnotableinthatitalsoincludedresearchontherarertypesofovariancancer,
suchasclearcell,endometrioid,germcell,smallcellcarcinomaoftheovaryhypercalcemictype
(SCCOHT),andmucinous.Nearlyalltheresearchpresentedwaspre-clinical,butmuchwaspromisingfor
theeventualdevelopmentoftherapiesintheseareas.
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ClearCell:Anumberofstudieswerereportedthatfollow-uponlastyear’sidentificationofthe
geneARID1Aasbeingmutatedin50%ofclearcellcarcinomas.Subsequentresearchhasfound
thatclearcellcarcinomaswithARID1Amutationsmaybesensitivetoaclassofdrugsthatinhibit
theproteinEZH2,whichregulatesthegrowthofcells.ThereareseveraldrugsforEZH2that
couldbeusedinfutureclinicaltrials,yetmoreworkremainstobedonetovalidatethese
findings.
Endometriod:Perhapssurprisingly,manyresearchershavefoundanumberofsimilarities
betweenclearcellandendometroidcancers,insomecasesevenfindingbothtumortypeinthe
samepatient.Thissuggeststhatthesetypesofcancersmightresultfromsimilarfactors,suchas
endometriosis.Itisnotyetknownifwomenthathavebothofthesetumortypeshadtheir
cancersdeveloponceorindependentlyfromeachother.
Germcelltumors:Researchersarelearningthatgermcelltumorsarefarmorerarethan
previouslythought,hintingthatmanywomenmayhavebeenmisdiagnosedwithgermcell
tumorsandperhapsgiveninappropriatetreatments.Thishighlightstheneedforbetter
diagnostictestsforgermcelltumorstoensurethatwomenreceivethecorrecttreatmentright
away.
SCCOHT:ResearchershaverecentlylearnedthatmostyoungwomenwithSCCOHThavea
mutationinthegeneBRG1intheirtumors.Researcherspresenteddataatthemeetingthat
identifiedaclassofdrugsthatmightbeeffectiveintreatingthem,butmuchmoreresearchis
neededtoverifythis.Incidentally,SCCOHTstillpuzzlesresearchersastheyaren’tsurehowit
develops.
Mucinous:Researchersarejuststartingtounraveltheoriginsofmucinousovariancancer
tumors,whichareveryrare.Iftheyareabletofindoutwhichtypesofalterationsaredriving
thesetumors,theymightbeabletomakeprogressintheirtreatment.Sofar,theyhaveafew
hintsthatmucinoustumorsmaybemoresimilartogastrictumors,thantheyaretoother
ovariancancertumors.
SharingthePatientExperience
Finally,theconferencealsofeaturedapaneldiscussionwithpatientadvocates–includingOCNA’sBoard
President,DianeRaderO’Connor,andSTSPresenter,CarlaJimenez.It’sworthnotingthattheaudience
consistedheavilyofbenchscientistswholikelydonotinteractwithpatientsonaroutinebasis.Ofthe
320+peopleinattendance,50%werePhDlevelscientists,20%werephysicians,25%weretraineeswho
don’tyethaveadvanceddegrees–andascantfew5%foradvocatesandsurvivors.
Inawidelyattendedandpopularsession,DianeandCarladiscussedtheirexperienceswithovarian
cancer,includinghowtheychosetheirdoctors,therapies,andwhetherornottoparticipateinaclinical
trial.Theconversationsdidn’tendattheendofthesession,though–DianeandCarlastayedonhandto
answerquestionsfromeagerresearchers,highlightingtheimportanceofopendialogbetweensurvivors
andscientists.