Clinical translation of       prostate cancer genomicsHenrik GrönbergProfessor Cancer Epidemiology,ChairmanDepartment of M...
Do I have prostate canceralternative how big is my risk to   I have been diagnosedget prostate cancer?                with...
ProstateProduceseminal fluidCreates problems- Prostate cancer- Hyperplasia- Prostatitis
Prostate cancer is common and a large challenge to clinical care          Prostate cancer is the most common           ca...
Do I have prostate canceralternative how big is my risk to   I have been diagnosedget prostate cancer?                with...
Through GWAS there are 75 loci identified associatedwith prostate cancer•     8q24 (8 separate loci)      Each SNP:•     1...
Today   Insensitive    • 2 of 3 positive tests are   diagnostics      incorrect   based on one   single         • 15-20% o...
Tomorrow                  • Enables screening to reduce                    prostate cancer mortality Improved diagnostics ...
The road to tomorrow : Randomized clinical trial• All men in Stockholm and  on Gotland between 50-69• Conducted 2013-2014 ...
All participants in STHLM3 will receive an answer                    • Low risk of prostate cancer          PSA < 1       ...
The expected patient and health economic value of STHLM3 isbig              Significant reduction of biopsies             ...
Do I have prostate canceralternative how big is my           I have been diagnosedpersonal risk to get prostate       with...
Today               We want to be able to identify                    the 30% that benefit from                    treatme...
•   Using gene expression score of 31                      cell cycle genes                  •   From FFPE samples        ...
The road to tomorrow 1(2)                             +        Panel of DNA and RNA markers differentiating the          t...
BUT, this is difficult !!!!!    STUDY DESIGN and    PROSPECTIVE VALIDATION     TUMOUR HETEROGENEITY     TECHNICAL ISSUES a...
Do I have prostate canceralternative how big is my           I have been diagnosedpersonal risk to get prostate       with...
Today   Situation after treatment    Not cured                               Everybody receives same                     C...
Tomorrow      • Non-cured identified directly and given        adjuvant treatment      • 75% receives feedback ”you are   ...
The road to tomorrow:Circulating tumor DNA – a promising personal biomarker              1                             2  ...
Three examples of possible use of genomic markers in the clinic      • Q1:Do I have prostate cancer alternative how big is...
AcknowledegementsKarolinska Institutet      CRISP-Center at Karolinska• Hans-Olov Adami          •   Per Hall             ...
Improved diagnostics and treatment of prostate cancer
Upcoming SlideShare
Loading in …5
×

Clinical translation of prostate cancer genomics, Department of Biosciences and Nutrition, Karolinska Institutet, Henrik Grönberg Copenhagenomics 2012

839 views

Published on

Clinical translation of prostate cancer genomics

0 Comments
1 Like
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total views
839
On SlideShare
0
From Embeds
0
Number of Embeds
2
Actions
Shares
0
Downloads
0
Comments
0
Likes
1
Embeds 0
No embeds

No notes for slide
  • OriginReason so good -&gt; qPCR sensitivity -&gt; investigate breakpoints rather than SNPsCaveats -&gt; Have to have access to the tumor Cancer heterogeneity 50 ng/ml and &lt;30% of that &lt;300 bp
  • Clinical translation of prostate cancer genomics, Department of Biosciences and Nutrition, Karolinska Institutet, Henrik Grönberg Copenhagenomics 2012

    1. 1. Clinical translation of prostate cancer genomicsHenrik GrönbergProfessor Cancer Epidemiology,ChairmanDepartment of Medical Epidemiology and Biostatistics (MEB)Karolinska Institutet, Stockholm, Sweden
    2. 2. Do I have prostate canceralternative how big is my risk to I have been diagnosedget prostate cancer? with prostate cancer, but do I really need treatment?I was diagnosed with prostatecancer and was treated, but am I I will be treated for mycured from the cancer? prostate cancer, which treatment is best for me?
    3. 3. ProstateProduceseminal fluidCreates problems- Prostate cancer- Hyperplasia- Prostatitis
    4. 4. Prostate cancer is common and a large challenge to clinical care  Prostate cancer is the most common cancer in the western world  Lifetime risk 10-15% and over 70.000 men in Sweden are living with prostate cancer today  Mortality is still substantial as 25% dies due to prostate cancer  Highest heritability of all cancers  PSA screening is very controversial
    5. 5. Do I have prostate canceralternative how big is my risk to I have been diagnosedget prostate cancer? with prostate cancer, but do I really need treatment?I was diagnosed with prostatecancer and was treated, but did I I will be treated against myreally get rid of my cancer? prostate cancer, which treatment is best for me?
    6. 6. Through GWAS there are 75 loci identified associatedwith prostate cancer• 8q24 (8 separate loci) Each SNP:• 17q12 (2)• 17q24.3 Odds Ratio 1,05-1,7• 3p12• 6q25 Common( 5-50%) in the population• 7p15• 10q11• 11q13 (2)• 19q13• Xp11• 18 NEW in September 2009 Aly et al 2011 (Euro Urology)• 35 NEW in 2011-2012 Using 35 SNPs 20-25% of prostate biopsies could be savedHenrik Grönberg 29 juni 2012 5
    7. 7. Today Insensitive • 2 of 3 positive tests are diagnostics incorrect based on one single • 15-20% of all high risk marker, PSA cancers are missed
    8. 8. Tomorrow • Enables screening to reduce prostate cancer mortality Improved diagnostics • Excludes 50% from further based on testing combination of 100+ markers • Significant reduction in un- necessary biopsies
    9. 9. The road to tomorrow : Randomized clinical trial• All men in Stockholm and on Gotland between 50-69• Conducted 2013-2014 Control arm• 260.000 men Clinical practice=PSA Prostate biopsyBest possible panel• PSA• 75+ SNPs Experimental arm• 8-10 protein biomarkers Best possible panel• Family history• Prediction Model
    10. 10. All participants in STHLM3 will receive an answer • Low risk of prostate cancer PSA < 1 50% • Testing is recommended in 10 years • Normal risk of prostate cancer Answer 35% PSA 1-3 • Testing is recommended in 2 years • Increased risk of prostate cancer 15% PSA < 3 • Biopsy is recommended
    11. 11. The expected patient and health economic value of STHLM3 isbig Significant reduction of biopsies Reduced number of non- aggressive cancers treated Identification of aggressive cancers earlier Significant reduction of health care cycle time Reduce anxiety – improved quality of life
    12. 12. Do I have prostate canceralternative how big is my I have been diagnosedpersonal risk to get prostate with prostate cancer, butcancer? do I really need treatment?I was diagnosed with prostatecancer and was treated, but did I I will be treated against myreally get rid of my cancer? prostate cancer, which treatment is best for me?
    13. 13. Today We want to be able to identify the 30% that benefit from treatment 70% survive without any treatmentSmall 10% dies despite treatmenttumors 20% survive thanks to treatment 12
    14. 14. • Using gene expression score of 31 cell cycle genes • From FFPE samples • Validated in 2 independent cohortsHenrik Grönberg 2012-06-29 13
    15. 15. The road to tomorrow 1(2) + Panel of DNA and RNA markers differentiating the tumors benefitting treatment from those not benefitting
    16. 16. BUT, this is difficult !!!!! STUDY DESIGN and PROSPECTIVE VALIDATION TUMOUR HETEROGENEITY TECHNICAL ISSUES and TUMOUR SAMPLING 15
    17. 17. Do I have prostate canceralternative how big is my I have been diagnosedpersonal risk to get prostate with prostate cancer, butcancer? do I really need treatment?I was diagnosed with prostatecancer and was treated, but did I I will be treated against myreally get rid of my cancer? prostate cancer, which treatment is best for me?
    18. 18. Today Situation after treatment Not cured Everybody receives same Cured treatment No adjuvant treatments 17
    19. 19. Tomorrow • Non-cured identified directly and given adjuvant treatment • 75% receives feedback ”you are completely healthy” 18
    20. 20. The road to tomorrow:Circulating tumor DNA – a promising personal biomarker 1 2 Analyze tumor’s Identify patient specific DNA post operation cromosome changes 3 4 Sample blood Measure circulating tumor- post treatment DNA in patients blood Behandling
    21. 21. Three examples of possible use of genomic markers in the clinic • Q1:Do I have prostate cancer alternative how big is my risk to get prostate cancer? SNPs + protein biomarkers Low-risk project and TTC (time to clinic) 2-3 years • Q2: I have been diagnosed with prostate cancer, but do I really need treatment? DNA and RNA based markers in FFPE tissue High-risk project and TTC 3+ ? years • Q3:I was diagnosed with prostate cancer and was treated, but did I really get rid of my cancer? Circulating tumor DNA in plasma High risk and TTC 6-24 months 20
    22. 22. AcknowledegementsKarolinska Institutet CRISP-Center at Karolinska• Hans-Olov Adami • Per Hall • Kamila Czene• Fredrik Wiklund • Sven Cnattingius• Katarina Bälter • Juni Palmgren• Carin Cavalli-Björkman • Juha Kere• Mikael Broms • Peter Wiklund• Johan Lindberg • Gunilla Svane• Markus Aly • Jan Adolfsson• Tobias Nordström • Yvonne Brandberg • Lars Egevad • Jan FrisellWake Forest Univ, NC• Jianfeng Xu• Lilly Cheng Human Protein Atlas , KTH • Jochen Schwenk • Mattias UhlenJohns Hopkins Hospital • Ulrika Igel• Bill IsaccsNamn Efternamn 2012-06-29 21
    23. 23. Improved diagnostics and treatment of prostate cancer

    ×