Engineering 25 bonus powerpoint oncotype dx (2)
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Transcript of Engineering 25 bonus powerpoint oncotype dx (2)
Genomic HealthOncotype DX
E25 Project Muthu Alagappan
Vaishnav Aradhyula
Pitch OutlineReview of Science
- Human Genome Project - Gene Expression and RT-qPCR
Introduction to Oncotype DXInnovations
- 21-gene panel including HER2
CLIA vs. FDAFuture Pipeline
Pitch OutlineReview of Science
- Human Genome Project - Gene Expression and RT-qPCR
Introduction to Oncotype DXInnovations
- 21-gene panel including HER2
CLIA vs. FDAFuture Pipeline
A Review of Personalized MedicineKnowledge of a patient’s genome can inform
treatmentCertain genomic traits predict the patient’s
susceptibility to diseaseSpecific treatments can be tailored to fit the
patient
From E25 Lecture 8
Gene ExpressionGene 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
cancerThus, measuring levels of gene expression is
a essential technique in understanding cancer
Measuring Gene ExpressionRT-PCR + qPCR (or RT-qPCR)
Generate cDNA template from mRNA using reverse transcription
Pitch OutlineReview of Science
- Human Genome Project - Gene Expression and RT-qPCR
Introduction to Oncotype DXInnovations
- 21-gene panel including HER2
CLIA vs. FDAFuture Pipeline
Oncotype DX – An OverviewDeveloped 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— BackgroundIncidence
270,000 cases of breast cancer per year in the U.S.
1.15 million per year worldwideTreatment
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 DXPhysicians 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 OutlineReview of Science
- Human Genome Project - Gene Expression and RT-qPCR
Introduction to Oncotype DXInnovations
- 21-gene panel including HER2
CLIA vs. FDAFuture Pipeline
How Oncotype DX Was Developed250 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) developedAlgorithm developed to assign Recurrence Score
(0 to 100) based on expression of the 21 genes
The 21 Genes
From Paik et. al
HER2HER2 (human epidermal growth factor receptor 2) is a tyrosine
kinase receptor protein that is over-expressed in aggressive forms of breast cancerLocation: Long arm of chromosome #17Mechanism: 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: 1. patients with HER2 expression have decreased survival rates2. HER2 over-expression is more likely to signal tumor
reoccurrence after surgery (75% chance vs 86%) 3. Used as 1 of 21 genes on our genetic panel (out of a potential
25,000 genes)
Oncotype DX in PracticeSubmit tissue sampleGenomic Health sends back RS score and
dataDoctor and Patient make informed decision
Pitch OutlineReview of Science
- Human Genome Project - Gene Expression and RT-qPCR
Introduction to Oncotype DXInnovations
- 21-gene panel including HER2
CLIA vs. FDAFuture Pipeline
FDA ProcessFood 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 4 phases of clinical trials
1988: Companies that do in vitro diagnostic testing in their laboratory now need to get CLIA approval.
Advantages of CLIA
Validation of Oncotype DXDoes a high recurrence score actually correlate to
recurrence?Test Oncotype DX against large sample to ensure
that it worksData 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 OutlineReview of Science
- Human Genome Project - Gene Expression and RT-qPCR
Introduction to Oncotype DXInnovations
- 21-gene panel including HER2
CLIA vs. FDAFuture Pipeline
Genomic Health PipelineGenomic Health other products
Colon 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 Clin Oncol. 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