Tony Dickherber NCI Center for Strategic Scientific Initiatives Outline The Innovative Molecular Analysis Technologies IMAT Program The Cancer Moonshot SM Initiative ITCR Annual PI Retreat ID: 813433
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Slide1
Collaboration Opportunities to Further Advance ITCR Platforms
Tony Dickherber
NCI, Center for Strategic Scientific Initiatives
Slide2Outline
The Innovative Molecular Analysis Technologies (IMAT) Program
The Cancer
Moonshot
SM
Initiative
ITCR Annual PI Retreat
Slide3Early-stage “wet-lab” technologies, with a broad technical scope and higher risk tolerance for potentially transformative technologies
>100 active projects (split between phase 1 and phase 2 stages of development) with 30-40 new projects launched each year
Two tracks:
Molecular/cellular analysis technologies
Biospecimen science technologies
Slide4General Breakdown of the IMAT Portfolio
Cancer Biology Technologies
Molecular fingerprinting (-
omic
discovery)
Molecular interactions
Cancer modeling
Imaging/spectroscopy probesSample preparationMechanobiololgy/microrheologyet cetera…
Technologies for Clinical Treatment and DiagnosisDrug screening platformsPatient-derived tumor modelingDiagnostic imaging agentsCancer-targetingDrug delivery vehiclesPoint-of-care diagnosticset cetera…
Early Detection ScreeningPoint-of-care detectionField sample collection and storageLiquid biopsy platformset cetera…
Molecular Epidemiology ToolsPopulation-scale analysisLow-resource setting point-of-care technologieset cetera…
Slide5119 Active Projects (66 R21 & 53 R33)
2018 PI Meeting Agenda
Molecular Pathway Tools
New Approaches for Sample Preparation and Preservation
miRNA Detection Approaches
Technologies to Improve Drug Discovery and Development
Next Generation Clinical Diagnostic Technologies
Cancer Modeling
Imaging ProbesSingle Cell Analysis TechnologiesAdvances in Mass SpectrometryNext PI Meeting @Cedar Sinai Medical CenterNov 22-24, 2019
Slide6Development of knowledge-driven
smMIP
assay for ultra-sensitive detection of clinically relevant variants in cancer
Expanding multiplexed kinase biosensor analysis to SWATH-MS
IMAT-ITCR Technology Collaboration Supplements
A Bioconductor Software Package for LISH-
seq
Probe Design and Data Analysis
Kasper Hansen, PhD
Tim Griffin, PhD
Laurie Parker, PhD
Obi Griffith, PhD
Steve Salipante, MD, PhD
Ben Larman, PhD
Imaging and informatics techniques to spatially map tumor-associated collagen: novel cancer diagnostic tools
Joel Saltz, MD
Richard Levenson, MD
Yun Wu, PhD
Noninvasive detection of circulating RNAs for monitoring early-stage non-small cell lung cancer recurrence and metastasis
Simina Boca, PhD
Tim Spicer, PhD
Ping Yang,
MD,PhD
Integration of 3D primary tumor drug-profiling with patient-specific drug gene networks for recommending targeted cancer therapies
R21
R21
R33
R33
R33
Phenotype Analysis Chip for isolation and multi-
omic
characterization of single cells with strongest and weakest ability in directional migration
Lidong Qin, PhD
R21
R33
Han Liang, MD
Slide7ITCR-IMAT Collaboration Supplement Opportunities
No dedicated funding to award supplements, but there may be administrative funds towards the end of the fiscal year.
Letter of Intent (LOI) due June 24, 2019
Must include at least 2 collaborating units (at least one
active IMAT project and at least one active ITCR project)~1 page expected (not to exceed 3 pages) – to include a brief overview for how the ITCR and IMAT projects complement each other and general goals of the collaboration.NCI budget availability assessment followed by response to selected LOIs by July 10, 2019. Full administrative supplement applications due by Aug 5, 2019.NOTE: Supplements cannot be awarded during periods of No Cost Extension!
Slide8https://innovation.cancer.gov
Slide9https://innovation.cancer.gov
Slide10https://innovation.cancer.gov
Slide11Outline
The Innovative Molecular Analysis Technologies (IMAT) Program
The Cancer
Moonshot
SM InitiativeITCR Annual PI Retreat
Slide12Blue Ribbon Panel Recommendations and Cancer Moonshot Implementation Teams
Network for Direct Patient Engagement
Cancer Immunotherapy Network
Overcome Drug Resistance
National Data Cancer Ecosystem
Drivers of Childhood Cancers
Symptom Management
Prevention and Early Detection
Human Tumor Atlases
Retrospective Analysis of Biospecimens
New Enabling Cancer Technologies
Pediatric Immunotherapy
Adult Immunotherapy
High Risk Cancers
Prevention & Screening
Slide13Recommendation I: Generation of Human Tumor Atlases
BRP Pediatric Cancer Working Group Report (pdf)
BRP Cancer Immunology Working Group Report (pdf)
BRP Tumor Evolution and Progression Working Group Report (pdf)
Final Blue Ribbon Panel Report (pdf)
Slide14The HTAN in the context of other “Atlas” initiatives:
Human Tumor Atlas Network
Emphasis on spatial relationships and interactions
Prospective/longitudinal sample collection (time)
Extensive clinical data
Atlases describing disease transitions
Slide15NUCLEAR
ORGANIZATION
We don’t yet know the best data, but it is sure to be multi-dimensional
Chromatin conformation (4C, Hi-C,
etc
), EM imaging
Whole genome, whole exome, targeted DNA
seq
Transcriptomics (RNA-
Seq
,
smFISH
, etc.); Epigenomics (ATAC-
Seq
)
Proteomics (many biochemical and imaging approaches)
Metabolomics (Mass spec, MALDI imaging, etc.)
Histology; Highly multiplexed 2D and 3D imaging
Medical imaging modalities (radiomics); circulating factors
Data Integration
Multi-scale modeling!
Many at single-cell resolution
Slide16Recommendation I: Generation of Human Tumor Atlases
Create dynamic 3D maps of human tumor evolution to document the genetic lesions and cellular interactions of each tumor as it evolves from a precancerous lesion to advanced cancer.
Adapted from “Cancer and the Human Tumor Atlas Network”
NCI’s Annual Plan and Budget for Fiscal Year 2020
Slide17HTAN Research Centers and Tumor Atlases
Colon
Skin
OHSU
Gray
/Goecks/
Mills/Corless
DFCI
Haining
/Regev
WUSTL
Ding
/Gillanders/
Achilefu/Fields
MSKCC
Pe’er
/
Icabuzio
-Donahue
Stanford
Snyder
/Ford
Vanderbilt
Coffey
/Lau/
Shrubsole
Harvard
Sorger
/
Santagata
/ Aster
Duke
Hwang
/Maley/West
Boston U
Spira
/
Dubinett
CHOP
Tan
/Hunger
HTAPP
FNLCR
/Broad
Pediatric
Cerami
(DFCI)/Shultz/Guinney/Reynolds
HTAN-DCC
PCAPP
MCL Consortium
Breast
Lung
Pancreas
Slide18ITCR algorithms and tools will be of great interest to the HTAN investigators:
… “Leveraging, where feasible, technology from related NCI-sponsored informatics initiatives, for example the NCI Informatics Technology for Cancer Research (
ITCR
) program, which supports the development of informatics algorithms, tools, and resources across the continuum of cancer research.” (from Moonshot RFAs)
Slide19At the end a successful 5-year HTAN effort, we expect a preliminary set of comprehensive human tumor atlases that:
Aid in defining tumor heterogeneity
within and across patients in high-priority adult and pediatric cancers
Quantify the dynamics and 3D architecture
of the tumor ecosystem during important transitionsFacilitate predictive modeling that leads to development of new risk stratification methods, better treatment options for patients, and improved understanding of disease mechanismsProvide direction for future atlas building efforts regarding the most impactful tumor atlas construction methods across tumor types
Expected outcome of the HTAN effort:
Slide20Blue Ribbon Panel Recommendations and Cancer Moonshot Implementation Teams
Network for Direct Patient Engagement
Cancer Immunotherapy Network
Overcome Drug Resistance
National Data Cancer Ecosystem
Drivers of Childhood Cancers
Symptom Management
Prevention and Early Detection
Human Tumor Atlases
Retrospective Analysis of Biospecimens
New Enabling Cancer Technologies
Pediatric Immunotherapy
Adult Immunotherapy
High Risk Cancers
Prevention & Screening
Slide21Multidisciplinary team science approach:
proteomics
structural biology
genomics/
epigenomics
medicinal chemistry
experimental therapeutics
cancer biology
To learn more about the
molecular mechanisms
of transformation driven by fusion oncoproteins and apply this knowledge to
target identification
,
small molecule inhibition
, and
pre-clinical testing
.
Cancer Moonshot Blue Ribbon Panel Recommendation E
Slide22The Center for Synovial Sarcoma Biology and Therapeutics
1U54CA231638-01
Kadoch (DFCI);
Shilatifard
(Northwestern)
An Integrated Approach to Analyze and Target EWS/FLI in Ewing Sarcoma
1U54CA231641-01
Lessnick
(Nationwide);
Darzacq
,
Tjian
(UC Berkeley)
Targeting SS18-SSX Biology in Pediatric Cancer
1U54CA231652-01
Jones, Cairns, Yap (Utah); Underhill, Nielsen (UBC); Lowe (MSKCC);
The Center for Therapeutic Targeting of EWS-oncoproteins
1U54CA231637-01
Stegmaier, Armstrong, Rivera, Gray, Fischer (DFCI);
Bushweller
(UVA); Kung (MSKCC); Sweet-Cordero (UCSF)
Slide23Highlights of the U54 Program
EWS-FLI (Ewing sarcoma):
Degradation-based strategies
Interactome
Domain analysisDownstream transcriptional output
Vulnerability screen
Role of EWS LCD
Role of microsatellitesIn vivo tools to study EWS/FLI under physiological conditions
SS18-SSX (synovial sarcoma):
Novel mouse modelsCell of origin studiesInteractomeDomain analysisInteracting chromatin proteins Relationship with BAF
Genome-wide studies of SS18-SSX bindingFeatures of accessible chromatinVulnerability screensWildtype SS18 stabilization
Slide24Expanding the Consortium in FY19
Fusion Sarcoma PAs
PPQs
Others
NCI Intramural
Other NCI funded grants
FusOnC
Admin
Supps
1st U54 solicitation (FY18):RFA-CA-17-0492nd
U54 solicitation (FY19): RFA-CA-19-006FY18 U54s:EWS/FLI1
SS18-SSX
FY19 U54s
Slide25Blue Ribbon Panel Recommendations and Cancer Moonshot Implementation Teams
Network for Direct Patient Engagement
Cancer Immunotherapy Network
Overcome Drug Resistance
National Data Cancer Ecosystem
Drivers of Childhood Cancers
Symptom Management
Prevention and Early Detection
Human Tumor Atlases
Retrospective Analysis of Biospecimens
New Enabling Cancer Technologies
Pediatric Immunotherapy
Adult Immunotherapy
High Risk Cancers
Prevention & Screening
Slide26Fusion Oncoprotein in
Childhood Cancer (FusOnC
2
) Consortium
PI-DDN
Pediatric Immunotherapy Discovery & Development Network
Moonshot Pediatric Core at
FNLCR
Immuno-Engineering to Improve Immunotherapy (i3) CentersNCI Cancer Research Data CommonsNCI Mouse Repository at FNLCR
Cancer Moonshot Immuno-Oncology Translation NetworkData Coordinating Center [U24]: Roswell Park (Hutson)10 Immunotherapy Teams [U01]
UC Irvine (Demetriou): Glycosylation ImmunotherapyDFCI (Kufe): Reversing Immune Evasion and IT ResistanceMoffitt (Conjeo-Garcia): Ovarian CancerNationwide Children’s (Bollard): Brain TumorsLJIAI
(Schoenberger):
H&N Cancer
UCLA
(Witte):
Small Cell Carcinomas
U WI
(Morris):
General Immuno-Radio Therapy
UCSD
(Sikora):
Oral Cancer Immuno-Radio Therapy
DFCI
(Van Allen):
Prostate Cancer
2 Immunoprevention Teams [U01]
MGH
(
Demehri
):
Breast Cancer
Cornell
(Lipkin):
Lynch Syndrome
In FY19, adding:
8-9 Immunotherapy U01s,
2-3 Immunoprevention U01s,
4-5
Immunoengineering
Centers
2-3 Immunoprevention Trials (UG3/UH3)
Slide27Cancer Moonshot Immuno-Oncology Translation Network
1 Collaboration Center
[U54]:
CHOP
(Maris) and Stanford (Mackall)
5 Project Teams
[U01]:
FHCC(Olson & Mehlin): NeuroblastomaU CO/CHOP (Fry & Tasian): High-Risk Acute Leukemias
CHOP/UPenn (Thomas-Tikhonenko & Barash): B cell malignanciesIUPUI/MSKCC (Paczesny & Cheung): TME targetingNationwide Children’s (Wang): Metabolic Reprogramming of the TMERFAs reissued and anticipating 1 more U54 center and up to 5 more U01 project teams in FY19
Fusion Oncoprotein inChildhood Cancer (FusOnC2) ConsortiumPI-DDNPediatric Immunotherapy Discovery & Development Network
Moonshot Pediatric Core at FNLCRImmuno-Engineering to Improve Immunotherapy (i3) Centers
NCI Cancer Research Data Commons
NCI Mouse Repository at
FNLCR
Slide28NCI Program Resources for Technology Enrichment
Small Business Innovation Research
(SBIR) Development Center
Administrative supplement for new moonshot collaborations
coming soonInnovative Molecular Analysis Technologies (IMAT) programCompetitive Revisions RFAs active in 2019-2020 ($150k DC/yr, 2 years)Informatics Technologies for Cancer Research (ITCR) program
Revisions to support the application of informatics technology to cancer research
coming soon
Cancer Tissue Engineering Collaborative (TEC) Research ProgramSupports the development and characterization of state-of-the-art biomimetic tissue-engineered technologies for cancer research.
Slide29Cancer Moonshot Technology Team
Goal
:
To identify areas where existing techniques and tools should (could?) be enhanced for projects in the network, and facilitate efforts to address those opportunities
. Encompasses improved laboratory through clinical capabilities, including novel platform technologies, model systems, reagents and techniques as well as software and other informatics tools. NCI activities: NCI to help making connectionsIdentify potential “matches” and introduce related investigators and envisaged possibilities
Identify active funding opportunities to support collaboration.
Facilitate exploratory workshops
to convene a diversity of disciplinary perspectives to sort through challenges establish connections with relevant groups for collaboration or otherwise share knowledgeexplore current state of the technology for a particular area of interestPossibly support new collaborationsLikely through small-scale grants to facilitate integration of an emerging platform or tool
Slide30Outline
The Innovative Molecular Analysis Technologies (IMAT) Program
The Cancer
Moonshot
SM InitiativeITCR Annual PI Retreat
Slide31Contact:
anthony.dickherber@nih.gov
(301) 547-9980
Slide32Extra Slides
Slide33Ongoing NCI Support for Technology Development
Affordable Cancer Technologies Program
Academic Industrial Partnerships
Slide34Ongoing NCI Support for Technology Development
Academic Industrial Partnerships
Affordable Cancer Technologies Program
>300 active SBIR phase 2 awards
10 R33 awards (~$1.4M
ea
)
~40 active awards across multiple phases (R21, U01, U24)
12 UG3 awards (~$2.6M
ea
)
>500 technologies available for Competitive Revisions (~35 new awards each year since 1998)
8 U01 and R01 awards (~$2.5M
ea
)
51 R01 awards spanning diagnosis and treatment technologies and for
in vivo
imaging systems
10 U54 centers &
10 U01 project awards
Slide35NCI Cancer Tissue Engineering Collaborative
Institution
Principal Investigators
Project Title
Boston University
Drs. Joe Tien and Celeste Nelson
Engineered Invasive Human Breast Tumors with Integrated Capilaries and Lymphatics
Brigham and Women’s Hospital
Drs. Ali Khademhosseini and Shiladitya SenguptaEngineering Personalized Micro-Tumor EcosystemsCleveland ClinicDrs. Emina Huang, Xiling Shen, & Michael ShulerAn Organotypic Model Recapitulating Colon Cancer Microenvironment and Metastasis
Harvard UniversityDrs. David Mooney, Jennifer Lewis, and F. Stephen Hodi3D Models of ImmunotherapyMassachusetts Institute of TechnologyDrs. Roger Kamm & David Barbie
Development of Physiologic Tissue Models to Assess Tumor Explant Response to Immune Checkpoint BlockadeUniversity of PittsburghDr. Shilpa SantThree-Dimensional Organoid Models to Study Breast Cancer Progression
University of Wisconsin
Drs. Pamela
Kreeger
, Kristyn Masters, and Paul
Campagnola
Engineered ECM platforms to analyze progression in high grade serous ovarian cancer
University of California, San Francisco
Drs. Manish K.
Aghi
& Sanjay Kumar
Modeling and Druggable-Genome Screening of Glioblastoma Invasion Using Regional Biopsy-Guided Biomaterials Systems
Slide36ex vivo models with human immune representation
David Barbie, M.D.
Medical Oncology
Roger Kamm, Ph.D.
Biomedical Engineering
Aref
et al
, Lab Chip, Sept 2018
“…ex vivo
diagnostic systems that recapitulate patient-specific tumor biology with the potential to predict response to immune-based therapies in real-time.”
Slide37Area C:
Functional microscale organotypic assays to predict patient response to anti-angiogenesis therapies
X. Sunney Xie, PhD
Area A: High Precision Single Cell Genomes: Linear Amplification and Digital Haplotypes
RFA-CA17-023:
Integration and Validation of Emerging Technologies for the Cancer Moonshot
[R33] –
Area A/C
Area C: Genome-wide identification and targeting of resistance to cancer therapy
Area A: Development of genetically tractable, driver gene-syngeneic brain tumor models for pre-clinical adoptive TCR-T therapy
Qijing
Li, PhD
Hai Yan, MD, PhD
Ryan Kelly, PhD
Eytan Ruppin, MD, PhD
J. Silvio Gutkind, PhD
David Beebe, PhD,
et al
Area A: Basic Research Tools
Area C: Cancer Modeling
Area A: In-Depth Proteome Mapping of the Tumor Microenvironment with Single-Cell Resolution
Slide38Amy Herr, PhD
Area B:
Advanced Cancer Classification via Single-Cell Electrophoretic Cytopathology
Area B:
Minimally Intrusive Colorectal Cancer Risk Stratification with
Nanocytology
: Targeting
Underscreened
PopulationsKrishna Nayak, PhD
RFA-CA17-023: Integration and Validation of Emerging Technologies for the Cancer Moonshot [R33] – Area B
David Mankoff, MD, PhD
Joel Karp, PhD
Hemant Roy, MD
Vadim Backman, PhD
Area B:
Molecular Beacon Based Extracellular mRNA and Protein Detection for Early Cancer Diagnosis
Martin Fleisher, MD
L James Lee, PhD
Area B:
Precise DCE-MRI Assessment of Brain Tumors
Area B: Clinical Technologies
Area B:
Multi-Tracer Volumetric PET (MTV-PET) to Measure Tumor Glutamine and Glucose Metabolic Rates in a Single Imaging Session
Slide39General Breakdown of the IMAT Portfolio
Cancer Biology Technologies
Molecular fingerprinting (-
omic
discovery)
Molecular interactions
Cancer modeling
Imaging/spectroscopy probesSample preparation
Mechanobiololgy/micro-rheologyet cetera…Technologies for Clinical Treatment and DiagnosisDrug screening platformsPatient-derived tumor modelingSample collection & preservation
Diagnostic imaging agentsCancer-targetingDrug delivery vehiclesPoint-of-care diagnosticset cetera…
Early Detection ScreeningPoint-of-care detectionField sample collection and storageLiquid biopsy platformset cetera…
Molecular Epidemiology Tools
Population-scale analysis
Low-resource setting point-of-care screening
et cetera…
Slide40Currently Active IMAT Portfolio
Slide41https://innovation.cancer.gov
Slide42https://innovation.cancer.gov
Slide43https://itcr.cancer.gov
Slide44https://itcr.cancer.gov