multi-modal analysis of distribution and efficacy of …©2017 mfmer | 3674401-1 multi-modal...
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©2017 MFMER | 3674401-1
Multi-modal analysis of distribution and efficacy of EGFR-targeted therapies in GBM
Jann N. SarkariaMIT/Mayo Physical Sciences Center for Drug Distribution and Efficacy in Brain Tumors
©2017 MFMER | 3674401-2
MIT/Mayo Physical Sciences Center for Drug Distribution and Efficacy in Brain Tumors
©2017 MFMER | 3674401-3
Is sub-therapeutic exposure bad?Mayo PDXs – GBM6, 12, 39
EGFR inhibitors
©2017 MFMER | 3674401-4
MALDI-MSI/MRI description of erlotinib distribution:GBM12
Randall et al., Nature Communications, 2018 in press
Erlo
tinib
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alAv
. Int
. m/z
394
.176
(a.u
.)
©2017 MFMER | 3674401-5
Physico-chemical parameters that influence drug distributionMALDI-MSI and Stimulated Raman Scattering
SRS: Protein – blue, lipid – greenMALDI-MSI: Erlotinib – pink
Randall et al., Nature Communications, 2018 in press
©2017 MFMER | 3674401-6
Impact of drug exposure on signallingRNAseq comparison of flank and intracranial tumors
Randall et al., Nature Communications, 2018 in press
Laser Capture RNAseq
Hig
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nial
©2017 MFMER | 3674401-7
Impact of sub-therapeutic drug exposure on signallingTyrosine phosphoproteomics
Randall et al., Nature Communications, 2018 in press
Plac
ebo
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dos
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©2017 MFMER | 3674401-8
Impact of brain penetration on efficacy of ADCDepatux-M (ABT-414)
GBM39 GBM108-VEGF
GBM108-vector
H&E TR-dextran H&E TR-dextran
GBM6
©2017 MFMER | 3674401-9
Radiomic predictors of genomics and drug distribution
©2017 MFMER | 3674401-10
Mayo RochesterKatie BakkenDebra BrinkmannDani BurgenskeTerry BurnsBrett CarlsonDavid DanielsPaul DeckerJeanette Eckel-PassowCaterina GianniniShiv GuptaLihong HeLori HenrichsZeng HuGaspar KitangeBianca MarinAndrea McMahonCole McKeanAnn MladekDeanna PafundiIan ParneyMark SchroederEmily SmithRachael Vaubel
Acknowledgments
Funding: MIT/Mayo Physical Sciences of Oncology Center; U54 CA210180
U of Minnesota Bill ElmquistMinjee KimGautham GampaJessica GriffithJanice LaramyAfroz MohammadKaren ParrishKatelyn SwansonSurabhi Talele
HarvardWalid AbdelmoulaNathalie AgarDavid CalligarisAmanda ClarkBegona Gimenez-Cassina LopezFrank LuElizabeth RandallMichael Reagan
MITAllison ClaasAntje DittmannBrian JoughinIshwar KohaleDoug LauffenburgerAlison TisdaleForest WhiteDane Wittrup
Mayo ScottsdaleKristin SwansonPamela JacksonAndrea Hawkins-DaarudSusan MasseyKamala Clark-SwansonScott WhitmireNhan TranMustafa TuncaliLeland HuGustavo deLeon
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