Engineering 25 bonus powerpoint oncotype dx (2)
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    Engineering 25 bonus powerpoint oncotype dx (2) Engineering 25 bonus powerpoint oncotype dx (2) Presentation Transcript

    • Genomic HealthOncotype DX
      E25 Project
      MuthuAlagappan
      Vaishnav Aradhyula
    • Pitch Outline
      Review of Science
      • Human Genome Project
      • Gene Expression and RT-qPCR
      Introduction to Oncotype DX
      Innovations
      • 21-gene panel including HER2
      CLIA vs. FDA
      Future Pipeline
    • Pitch Outline
      Review of Science
      • Human Genome Project
      • Gene Expression and RT-qPCR
      Introduction to Oncotype DX
      Innovations
      • 21-gene panel including HER2
      CLIA vs. FDA
      Future Pipeline
    • 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
    • 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
    • Measuring Gene Expression
      RT-PCR + qPCR (or RT-qPCR)
      Generate cDNA template from mRNA using reverse transcription
    • Pitch Outline
      Review of Science
      • Human Genome Project
      • Gene Expression and RT-qPCR
      Introduction to Oncotype DX
      Innovations
      • 21-gene panel including HER2
      CLIA vs. FDA
      Future Pipeline
    • 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
    • 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
    • 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
    • Pitch Outline
      Review of Science
      • Human Genome Project
      • Gene Expression and RT-qPCR
      Introduction to Oncotype DX
      Innovations
      • 21-gene panel including HER2
      CLIA vs. FDA
      Future Pipeline
    • 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
    • The 21 Genes
      From Paik et. al
    • 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)
    • Oncotype DX in Practice
      Submit tissue sample
      Genomic Health sends back RS score and data
      Doctor and Patient make informed decision
    • Pitch Outline
      Review of Science
      • Human Genome Project
      • Gene Expression and RT-qPCR
      Introduction to Oncotype DX
      Innovations
      • 21-gene panel including HER2
      CLIA vs. FDA
      Future Pipeline
    • 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.
    • FDA Approval Phases
    • 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
    • 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
    • Recurrence Score is an Excellent Predictive Tool
      From Paik et. al
    • Pitch Outline
      Review of Science
      • Human Genome Project
      • Gene Expression and RT-qPCR
      Introduction to Oncotype DX
      Innovations
      • 21-gene panel including HER2
      CLIA vs. FDA
      Future Pipeline
    • Genomic Health Pipeline
      Genomic Health other products
      Colon cancer
      Prostrate cancer
      Renal cancer
    • 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