Preparing for the unknown Future translational opportunities David - - PowerPoint PPT Presentation
Gynecologic Cancer InterGroup Translational Research Brainstorming October 2016 Lisbon Preparing for the unknown Future translational opportunities David Huntsman COI disclaimer Relationships with commercial
Gynecologic Cancer InterGroup Translational Research Brainstorming October 2016 Lisbon
Gynecologic Cancer InterGroup Translational Research Brainstorming October 2016 Lisbon Outline The last five years- major translational research opportunites, what is required and what can be learned Tissue based proteomics to support translational research Biobanking for tomorrows opportunities: is this too much to ask?
1-- Some technologies like full gene resequencing get reduced to practice to work on FFPE 2– Some technologies particularly those which require well preserved dissaggregated or living cells are unlikely to scale 3- Full genome analtsis creates complex and large datasets that can be rendered near-uninterpretable by the predictable artefacts of standard fixation thus best done in frozen material 4- Some opportunites like cell free DNA analysis require new samples types but they are easily obtained without large deviations from normal lab practice
What about proteomics? Proteomics has not been used in many clinical trials as it has not been reduced to practice –frozen samples have been needed and tissue amounts beyond what can be acheived clinically Tissue based CyTOF and other antibody based in-situ mass spec analysis show promise but are labor and time intensive We have proof of principle for full proteome sceening of FFPEC materials (Hughes et al Sci Reports 2016)
0 = no staining 1 = weak or variable staining 2 = strong, diffuse staining
Methionine Homocysteine Cystathionine Cysteine
Glutathione
CCOC ENOC HGS
CTH CBS a-Tubulin A2780 IGROV1 TOV112D 2008 JHOC5 JHOC7 JHOC9 OVISE OVMANA OVTOKO RMG2 TOV21G CaOV3 Hey Kuramochi CaOV3 Hey OVCAR 3 OVCAR 4 OVCAR 5 OVSAYO
Homocysteine Cystathionine Cysteine
Endometrium Fallopian Tube
Gynecologic Cancer InterGroup Translational Research Brainstorming October 2016 Lisbon INSERT PROGNOSIS SLIDE
A motivated team can have high accrual rates Generic approvals with secondary project specifc applications possible Intensive acivities such as establishing xenografts or collection multiple biopsies (spatial or temporal) possible Success is due to voluntary efforts of mutually interested parties which helps control costs Best source of high quality materials but not expandable without great expense
Biospecimen collection: National and International collections Very expensive to establish biobanks in sites where there is no interest in translational research –such top down efforts are unlikely to be flexible enough to rapidly embrace new opportunites such as cell free DNA collection Extensive collections of QA’d frozen or FFPE material can be aggregated from pre-existing collections (OTTA and TFRI Couer) – approach not that useful for trials
It would seem reasonable that appropriate consent and banking FFPE tumour, Normal DNA from cheek swab of blood, and even collection of samples for cell free DNA analysis should be possible in all sites engaged in modern clincial trials – such materials will be useful for most common translational needs Other more demanding but useful collections such as living or fresh frozen materials or biosies from multiple time points on study could be collected by leading research sites within studies and perhaps used for hypothesis generating experiements with validation (post reduction to practice) performed on samples from the rest of the study Note: full scale proteomics is possible from FFPE with IHC providing a natural validation strategy