Download Ovarian Cancer Australia Webinar “What is ovarian cancer”?

OvarianCancerAustralia
Webinar
“Whatisovariancancer”?
Ovariancancer–howwearege:ng
toknowtheenemy
ProfessorDavidBowtell
PeterMacCallumCancerCentre,Melbourne
GarvanInsGtuteandKinghornCancerCentre,Sydney
[email protected];[email protected]
Talkoutline
•  Recognizingthedifferenttypesofovariancancer
•  Genesthatinfluencetheriskofdevelopingovarian
cancer
•  Genesthatinfluencetheresponseofthe
cancertotreatment
•  Thedevelopmentofdrugresistant
cancerswiththerapy
Talkoutline
•  Recognizingthedifferenttypesofovariancancer
•  Genesthatinfluencetheriskofdevelopingovarian
cancer
•  Genesthatinfluencetheresponseofthecancerto
treatment
•  Thedevelopmentofdrugresistantcancerswith
therapy
CancerdiagnosishasbeenbasedonlocaGon
inthebodyandpaSernsofcellgrowth
Ovariancancerisacomplexdisease
•  Germcelleg.
dysgerminoma
•  Sexcord–stromal/
carcinoma
•  Epithelial
(90%)
C.Kosary(2007)Cancersoftheovary(Chapter16:SEERSurvivalMonograph)
ConvenGonalclassificaGonof
epithelialovariancancer
6
10
12
15
60
Serous
Mucinous
Endometrioid
Clearcell
Other
OvarianSurface
Epithelium
Themostcommontypesofovariancancerwere
thoughttomostlyarisefromcellsonthesurface
oftheovary
OvariancancerisaseriesofdisGnct
diseaseswithdifferentcellsoforigin
–mostlynotfromtheovaryandallverydifferent!
Vaughan et al (2011) Nature Reviews Cancer
WhythereclassificaGonofovarian
cancerisimportant:
• Treatmentsneedtobespecific–notaonesizefitsall
• GeneGcrisktrackswithspecifictypes–helpsdecidewho
shouldbeofferedtesGng
• Wecan’tfigureoutthebiologyiftheyare
allmixedtogether
• Knowingwheretheycomefrominfluences
prevenGon(eg.removaloffallopiantubes)
andearlydetecGonstrategies
Refocusingriskreducingsurgeryin
womenwithBRCA1orBRCA2
mutaGons
•  Removalofovariesandfallopian
tubestogether?
•  Removaloffallopiantubesonlyas
thisiswherecancersassociated
withBRCAmutaGonsarise?
•  Fallopiantubesfirst
andovarieslater?
OvarianclearcellcancergeneGcmake
upresemblesrenalclearcellcancer!
sunitinib
Surgery +
Platinum - taxol
SuniGnibisusedinrenalcancer
Anglesio et al (2011) Clinical Cancer Research
Talkoutline
•  Recognizing the different types of ovarian cancer
•  Genesthatinfluencetheriskofdevelopingovarian
cancer
•  Genes that influence the response of the cancer to treatment
•  The development of drug resistant cancers with therapy
First,whatexactlyisagene?
OurgenomeismadeofDNApackaged
intochromosomes
chromosomes
A
G
T
T
C
DNA
T
G
OvariancancergeneGcs
TheBRCA1andBRCA2genesprovide
theblueprintsforcomponentsofa
nanomachinethatveryaccurately
repairsDNA
BRCA1andBRCA2mutaGonsincreasethe
riskofbreastandovariancancerby10-20X
BRCA1/2makeproteinsthatareinvolvedinDNArepair
Lossofonecopy(mutaGon)increasestheriskofbreastandovarian
cancer(alsosomeothercancers,eg.prostatecancerinmen)
MutaGonfrequencywasthoughttobe5-10%
TesGngwasofferedbasedonstrongfamilyhistory(andageof
diagnosis)
Studiesaroundtheworld,includingamajor
Australianstudychangedthatview
BRCAmutaGonsinovariancancer
Whatwastherealfrequencyof
mutaGon?
17%ofhighgradeserouscancers
Almostonlyseeninthese
cancers
ShouldthegeneGctesGng
guidelinesbechanged?
Yes.Almosthalfofthecarriers
didn't haveafamilyhistory–so
wouldbemissed.Guidelines
nowchanged
DidcarryingamutaGoninfluence
treatment?
Yes.BeSerresponsetotreatment
andbeSersurvival.Persistwith
plaGnum.
Isitusefultoknow?
Yes.Riskof
ovariancancer
canbereduced
by80-90%
Alsop et al (2012) Journal of Clinical
Oncology
Talkoutline
•  Recognizing the different types of ovarian cancer
•  Genes that influence the risk of developing ovarian cancer
•  Genesthatinfluencetheresponseofthecancerto
treatment
•  Thedevelopmentofdrugresistantcancerswiththerapy
Nature May 2015
95 trillion bits of data
Understanding
excepGonalresponse
• 
• 
• 
• 
InternaGonalconsorGum(US,Canada,UK,Australia,Scandinaviancountries)
Australialeadsthegenomesequencinganalysis
Womenwithadvancedhighgradeserousovariancancerwhosurvive>10years
RecentlyfundedbyUSDepartmentofDefense
Genetic (germline and in the cancer)
Lifestyle
Immune
Summary
WehaveamuchbeSerideaofhowthedifferenttypes
sortout–specifictherapies,notonesizefitsall
GeneGcsisclearer–changethetesGngguidelines
CompleteblueprintofallthemutaGonsincommon
(andrare)forms–knowwhatwearedealingwith
andcanseenewtargets
Recurrenceandacquiredresistance–criGcal
weunderstandthis