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Cancer Genomics Coming up to Speed

Cancer Genomics Coming up to Speed. NCI Cancer Center Directors April 19, 2012. NCI Cancer Genomics 2012-> 2018 . DISCOVERY by genomics and functional genomics. Pathway Function. DNA-based Diagnosis. Drug Development. Precision Treatment . Present / Future TCGA, TARGET, CTD2.

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Cancer Genomics Coming up to Speed

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  1. Cancer Genomics Coming up to Speed NCI Cancer Center Directors April 19, 2012

  2. NCI Cancer Genomics 2012-> 2018 DISCOVERY by genomics and functional genomics Pathway Function DNA-based Diagnosis Drug Development Precision Treatment Present / Future TCGA, TARGET, CTD2

  3. Cancer Genome Conclusion 1 One tumor type -> different driver genes/mutations

  4. Conclusion 2 Many tumor types per gene, per pathway, per drug Argues for off-label use of drugs based on genomic typing rather than histopathological typing

  5. Conclusion 3 Tumors are highly combinatoric for driver genes 0.7 x 0.5 x 0.3 = 0.1 Additional genetic combinatorics from metastasis 0.5 X 0.3 = .15 treatment side effect allele 0.5 resistance 0.2 Frequency = 0.0015 >> We therefore need to learn from 105 – 107 cases TCGA is only 500 cases of each histo-type type NCI Cancer Centers opportunity to lead......

  6. Clinical Cancer genomics can/should drive more and deeper discovery Invent new patient status: “Cancer Information Donor” To capture shared knowledge from those who donate de-identified genomic & clinical data Hopeful and essential goal, but challenges to implement Can NCI Cancer Centers be at the forefront?

  7. Three Classes of Genome Diagnostics 1. Genome-derived specific tests: i.e. EGFR 2. “Actionable” gene panels (drivers): 10’s – 100’s 3. Full Genome-Driven Diagnosis whole exomes whole transcriptomes genomes sequenced In your centers, what to translate when, to whom, and who learns the outcomes?

  8. What should our immediate future be? What do other 1st world efforts teach?

  9. For “Genome Informed” Studies: DNA/RNA information obtained during trials and from archival samples Working proposition for 2013: Every NCI-funded trial will require genomic samples & consents • Made possible by FFPE sample improvement -> DNA/RNA sequencing • Require genomic data to be deposited in timely manner in appropriate database for entire research community

  10. For “Genome DRIVEN” treatment • Genomic testing to guide treatment • Patients increasingly demandthis • Working propositions to consider / refine / replace: • 1. Establish minimum genome diagnostic panel (s) for all • NCI Cancer Center patients – revise annually • 2. Create and cultivate “Cancer Information Donor” • Apply coherent informed consent • Return information (de-identified) to national database

  11. Translational Genomics Elsewhere: Consider France

  12. Arul Chinnaiyan, William Pao, Elaine Mardis

  13. French path to consolidate QA/QC based on results from their multiple (28) centers

  14. NCI Cancer Genomics DISCOVERY by genomics and functional genomics Pathway Function DNA-based Diagnosis Drug Development Precision Treatment Present / Future TCGA, TARGET, CTD2

  15. photo: Josh Lewandowski

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