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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 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
Cancer Genome Conclusion 1 One tumor type -> different driver genes/mutations
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
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......
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?
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?
What should our immediate future be? What do other 1st world efforts teach?
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
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
Arul Chinnaiyan, William Pao, Elaine Mardis
French path to consolidate QA/QC based on results from their multiple (28) centers
NCI Cancer Genomics DISCOVERY by genomics and functional genomics Pathway Function DNA-based Diagnosis Drug Development Precision Treatment Present / Future TCGA, TARGET, CTD2