Engineering 25 bonus powerpoint oncotype dx (2)

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  • 1. Genomic HealthOncotype DX
    E25 Project
    MuthuAlagappan
    Vaishnav Aradhyula
  • 2. Pitch Outline
    Review of Science
    • Human Genome Project
    • 3. Gene Expression and RT-qPCR
    Introduction to Oncotype DX
    Innovations
    • 21-gene panel including HER2
    CLIA vs. FDA
    Future Pipeline
  • 4. Pitch Outline
    Review of Science
    • Human Genome Project
    • 5. Gene Expression and RT-qPCR
    Introduction to Oncotype DX
    Innovations
    • 21-gene panel including HER2
    CLIA vs. FDA
    Future Pipeline
  • 6. A Review of Personalized Medicine
    Knowledge of a patient’s genome can inform treatment
    Certain genomic traits predict the patient’s susceptibility to disease
    Specific treatments can be tailored to fit the patient
    From E25 Lecture 8
  • 7. Gene Expression
    Gene expression is the conversion of information encoded by a gene into a functional gene product (usually proteins)”
    Certain genes (and thus certain proteins) are often found to be overexpressed in several types of cancer
    E.g. HER2 overexpression is linked to breast cancer
    Thus, measuring levels of gene expression is a essential technique in understanding cancer
  • 8. Measuring Gene Expression
    RT-PCR + qPCR (or RT-qPCR)
    Generate cDNA template from mRNA using reverse transcription
  • 9. Pitch Outline
    Review of Science
    • Human Genome Project
    • 10. Gene Expression and RT-qPCR
    Introduction to Oncotype DX
    Innovations
    • 21-gene panel including HER2
    CLIA vs. FDA
    Future Pipeline
  • 11. Oncotype DX – An Overview
    Developed by Genomic Health, a life science company based in Redwood City and founded in 2000
    Oncotype DX is a diagnostic test for breast cancer
    Analyzes 21 genes from a breast cancer tumor to determine the likelihood of recurrence and the effectiveness of chemotherapy
  • 12. Oncotype DX— Background
    Incidence
    270,000 cases of breast cancer per year in the U.S.
    1.15 million per year worldwide
    Treatment
    Previous treatments based mainly on understanding of chemical pathways
    Tamoxifen and chemotherapy proven to be reasonably effective in clinical trials
    However, chemotherapy overused because not possible to determine the risk of recurrence
  • 13. Clinical Need for Oncotype DX
    Physicians require a diagnostic tool that:
    Quantitatively states the chances of recurrence (as opposed to “high” or “low”)
    Known as prognostic significance
    Indicates whether the patient will significantly benefit from chemotherapy
    Known as predictive significance
    Important because of chemotherapy’s severe side effectss
  • 14. Pitch Outline
    Review of Science
    • Human Genome Project
    • 15. Gene Expression and RT-qPCR
    Introduction to Oncotype DX
    Innovations
    • 21-gene panel including HER2
    CLIA vs. FDA
    Future Pipeline
  • 16. How Oncotype DX Was Developed
    250 candidate genes (from ~25,000 genes in the human genome) identified from literature and previous studies
    The gene expression of these genes relative to control genes measured against recurrence in 477-patient sample
    16 genes identified
    21 gene test (16 cancer-related genes and 5 reference genes) developed
    Algorithm developed to assign Recurrence Score (0 to 100) based on expression of the 21 genes
  • 17. The 21 Genes
    From Paik et. al
  • 18. HER2
    HER2 (human epidermal growth factor receptor 2) is a tyrosine kinasereceptor protein that is over-expressed in aggressive forms of breast cancer
    Location: Long arm of chromosome #17
    Mechanism: HER2 and HER3 dimerize on cell membrane. Growth factor binds and causes cell proliferation.
    Significance: 30% of breast cancers have an over-expression of HER2. Also linked to ovarian and stomach cancer.
    Drug herceptin can reduce the expression of HER2
    Impact:
    patients with HER2 expression have decreased survival rates
    HER2 over-expression is more likely to signal tumor reoccurrence after surgery (75% chance vs 86%)
    Used as 1 of 21 genes on our genetic panel (out of a potential 25,000 genes)
  • 19. Oncotype DX in Practice
    Submit tissue sample
    Genomic Health sends back RS score and data
    Doctor and Patient make informed decision
  • 20. Pitch Outline
    Review of Science
    • Human Genome Project
    • 21. Gene Expression and RT-qPCR
    Introduction to Oncotype DX
    Innovations
    • 21-gene panel including HER2
    CLIA vs. FDA
    Future Pipeline
  • 22. FDA Process
    Food and Drug administration used to evaluate and approve new medical devices, drugs, and diagnostics test
    1976: FDA passes amendments which allowed “homebrew in vitro diagnostics” to come to market without FDA approval (because all testing would be done by the company within their own laboratory)
    FDA approval requires 3 phases of clinical trials
    1988: Companies that do in vitro diagnostic testing in their laboratory now need to get CLIA approval.
  • 23. FDA Approval Phases
  • 24. Advantages of CLIA
    CLIA is the Clinical Laboratory Improvement Amendment
    Objective: to guarantee the accuracy and reliability of diagnostic testing of patient tissue performed by laboratories
    CLIA does not require any clinical trials. Instead, it only requires an application, evaluation, and payment.
    Advantage: CLIA can save Genomic Health millions of dollars and years of time from clinical trials
    Downside: Clinical trials are sometimes necessary to convince physicians of the advantages of the diagnostic
  • 25. Validation of Oncotype DX
    Does a high recurrence score actually correlate to recurrence?
    Test Oncotype DX against large sample to ensure that it works
    Data taken from
    National Surgical Adjuvant Breast and Bowel Project (NSABP) trials B-14 and B-20
    Trials assessed effectiveness of Tamoxifen
    2892 patients randomly assigned to Tamoxifen or placebo
    Statistical Analysis of recurrence score versus actual recurrence reveals that the Oncotype DX assay is a very good predictive tool
  • 26. Recurrence Score is an Excellent Predictive Tool
    From Paik et. al
  • 27. Pitch Outline
    Review of Science
    • Human Genome Project
    • 28. Gene Expression and RT-qPCR
    Introduction to Oncotype DX
    Innovations
    • 21-gene panel including HER2
    CLIA vs. FDA
    Future Pipeline
  • 29. Genomic Health Pipeline
    Genomic Health other products
    Colon cancer
    Prostrate cancer
    Renal cancer
  • 30. Bibliography
    Paik, S et. al. A Multigene Assay to Predict Recurrence of Tamoxifen-Treated, Node-Negative Breast Cancer. N Engl J Med. 351;27. 30 Dec 2004
    http://ecog.dfci.harvard.edu/general/gendocs/tailorx_oncodxfact.pdf
    http://www.oncotypedx.com/en-US/Breast/HealthcareProfessional/Overview.aspx
    Sparano, JA and Paik, S. Development of the 21-Gene Assay and Its Application in Clinical Practice and Clinical Trials. J ClinOncol. 2008; 26:721-728.
    http://en.wikipedia.org/wiki/Gene_expression
    http://www.genomichealth.com/en-US/Pipeline/NextGeneration.aspx
    http://www6.appliedbiosystems.com/support/tutorials/pdf/rtpcr_vs_tradpcr.pdf
    http://www.genomichealth.com/en-US/Company.aspx