o nco p anel and profiling services therapeutic strategies ... … · o nco p anel cell-based...
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PHARMA PHARMA PHARMA PHARMA PHARMA DISCOVERY DISCOVERY DISCOVERY DISCOVERY EXPERTISE EXPERTISE EXPERTISE EXPERTISE PHARMA PHARMA PHARMA PHARMA PHARMA DISCOVERY DISCOVERY DISCOVERY DISCOVERY
PHARMA PHARMA PHARMA PHARMA PHARMA DISCOVERY DISCOVERY DISCOVERY DISCOVERY EXPERTISE EXPERTISE EXPERTISE EXPERTISE PHARMA PHARMA PHARMA PHARMA PHARMA DISCOVERY DISCOVERY DISCOVERY DISCOVERY
PHARMA PHARMA PHARMA PHARMA PHARMA DISCOVERY DISCOVERY DISCOVERY DISCOVERY EXPERTISE EXPERTISE EXPERTISE EXPERTISE PHARMA PHARMA PHARMA PHARMA PHARMA DISCOVERY DISCOVERY DISCOVERY DISCOVERY
PHARMA PHARMA PHARMA PHARMA PHARMA DISCOVERY DISCOVERY DISCOVERY DISCOVERY EXPERTISE EXPERTISE EXPERTISE EXPERTISE PHARMA PHARMA PHARMA PHARMA PHARMA DISCOVERY DISCOVERY DISCOVERY DISCOVERY
OncoPanel™ CELL-BASED SCREENING AND PROFILING SERVICESTherapeutic Strategies for Oncology with Cellular and Genomic Profiling
Eurofins Discovery.Deep resources for success.
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A ROBUST DRUG RESPONSE PLATFORM WITH CUSTOM OPTIONS TO DRIVE ONCOLOGY THERAPEUTIC DISCOVERY AND DEVELOPMENT, OFFERED EXCLUSIVELY BY Eurofins Discovery.
Over 300 2D and 100 3D spheroid human cancer cell line models drive design of epigenetic, kinase, gene family, and target-focused expression panels, making thorough candidate assessment possible.
OncoPanel HUMAN-CENTERED DATA POWERS A MORE TARGETED AND EFFICIENT CLINICAL TRIAL DESIGN.
Use OncoPanel profiling to improve patient stratification prior to clinical trial launch. Early identification of genomic biomarkers of response provides insights on genomic features that may predispose patients to therapeutic responses or identify potential resistance mechanisms.
OncoPanel™ CELL-BASED SCREENING AND PROFILING SERVICES
Flexibility and expertise to suit your oncology program needs
300+ Cancer Cell Lines
80+ Clients
60+ Reference Benchmark Compounds
19 Distinct Tissue Lineages
274,000 Genetic Aberrations
100+ Spheroid Models
10+ Years Experience
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COMPREHENSIVE ASSESSMENT WITH DEPTH AND BREADTH INFORMS ON TEST AGENT POTENCY, TISSUE LINEAGE SENSITIVITY, GENOMIC ALTERATIONS, AND RESISTANCE STRATIFICATION.
Figure 3. Identification of mutations associated with sensitivity or resistance to Nutlin-3 (an MDM2 inhibitor) treatment of OncoPanel human tumor cell lines.
0.50.4
0.30.20.1
-0.10
-0.2-0.3-0.4-0.5
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-0.8-0.9
-15 -10 -5 0 5 10 15 20 25
Odds Ratio
Effe
ct
Resistance
Sensitivity
• Reveal statistically significant genomic features – including amplifications, mutations, deletions, and differential gene expression – associated with drug sensitivity or resistance
• Confirm in vitro the results of test agent profiling or screening outcomes
• Rank test agents for further lead optimization
Figure 2. Impact of the BRAF inhibitor vemurafenib on cell proliferation across 300+ human cancer cell lines representing 18 different tissue types/subtypes—as revealed by OncoPanel screening.
Skin
(Mel
anom
a)C
olon
Soft
Tiss
ues
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crin
eSt
omac
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ver
Cen
tral N
ervo
usSy
stem
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atop
oiet
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ncre
asKi
dney
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der
Fem
ale
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st
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enta
Pros
tate
Eye
Hea
d an
d N
eck
1.5
1.0
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-0.5
-1.5
-1.0
Log 10
IC50
• Differentiate tissue and tumor lineage types most sensitive to drug or combination approaches
• Identify therapeutic oncological indications for maximal potential clinical efficacy
• Rank tissue types based on cell viability, proliferation, apoptosis induction, and cell cycle arrest
Figure 1. Example drug response curves with half maximum effective concentration (EC50), half maximal inhibitory concentration (IC50), and half maximal inhibition of cell growth (GI50).
Cel
l Cou
nt, %
Con
trol
Compound, µM
100
75
50
GI50
T0IC50EC50
25
0
Curve Bottom
0% Control
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MAXIMUM FLEXIBILITY WITH STANDARD AND CUSTOM OPTIONS
Profile test agents, or test agent combinations, in the comprehensive, 300+ cell line panel or in smaller lineage-type or gene-specific subpanels of interest. All cell lines are licensed from ATCC, Memorial Sloan-Kettering, or other commercial vendors ensuring freedom to operate, are kept at low passage, and are consistently monitored for growth characteristics to ensure robust, reproducible responses.
For a complete and up-to-date list of available cell lines and genetic targets, please contact [email protected]
BRING THE POWER OF GENOMIC ANALYSIS TO YOUR DRUG DISCOVERY AND DEVELOPMENT EFFORTS
Figure 4. Pie chart of 19 different tissue or tumor lineage types represented in OncoPanel.
EXPANDED INSIGHTS WITH 3D SPHEROID MODELS
Spheroids offer certain advantages over 2D models, including representation of solid tumor hypoxia, pH, and nutrient gradients. Over one hundred cancer cell lines are available as 3D models in a customizable assay format, with up to seven days drug exposure options.
Figure 5. Spheroid models of four different tumor cell lines imaged at 10X magnification under brightfield illumination prior to test agent addition, as part of routine QC processes.
Lymphoma
Colon
Lung
Central Nervous System
Skin
Leukemia
Female GU
Soft Tissue & Bone
Breast
Pancreas
Bladder
Head and Neck
KidneyEndocrine
Liver
ProstateStomach
MyelomaOther
Target Class Gene ExamplesKinases BRAF, FLT3, PIK3CA
Growth factor receptors EGFR, IGF1R, MET
G-protein coupled receptors CNR1/CNR2, DRD2, SMO
Ion channels ABCC9, KCNH2, KCNK2
Transcription factors ESR1, MYC, STAT3
Enzymes KRAS, PARP1, TNKS
Epigenetic targets BRD4, EZH2, HDAC1
25,000+ genes available for creation of custom cell panels to inform on test agent impact.
A-673 Ewing’s sarcoma
G-361 Melanoma
LS411N Colorectal carcinoma
PC3Prostate adenocarcinoma
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IDENTIFY MARKERS PREDICTIVE OF TREATMENT RESPONSE
The OncoPanel™ platform uniquely offers extensive genomic analysis of human cancer cell line drug responses. Detailed genomic information allows for the statistical correlation of test responses (both sensitivity and resistance) with specific genomic features, such as mutations or copy number variations, to inform on patient stratification.
IDENTIFY PATHWAYS OR PROCESSES IMPLICATED IN DRUG RESPONSES
For defined pathway mechanisms, differential gene expression analysis can provide insights into individual biomarkers for further evaluation and potential asset repositioning.
Figure 6. A database of genomic features evaluated for correlation to PD0325901 responsiveness, as measured by cell count IC50. Use of orthogonal Student’s t-test (x axis) and Fisher’s exact test (y axis) address mathematical bias, allowing identification of biologically relevant features significant by both. Genomic features satisfying both significance thresholds, and with q-values (FDR) <0.1, are colored dark green and annotated.
Figure 7. A. Volcano plot showing differentially expressed genes associated with resistance or sensitivity to Nutlin-3 inhibition of MDM2 activity. MDM2 is an E3 family ubiquitin ligase. B. Pathway analysis of differentially expressed genes identified in response to Nutlin-3 treatment.
A B
-Log
10 P
-Val
ue
Fold Change
Resistant Sensitive
1% FDR
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signal transduction by p53 class mediator
intrinsic apoptoticsignaling pathway by p53 class mediator
cellular response to stress
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
mitotic DNA damage checkpoint
intrinsic apoptotic signaling pathway in response to DNA damage
DNA damage checkpoint
DNA integritycheckpoint
mitochondrion organization
response to UV
mitotic DNA integrity checkpoint
response to stress
p53 signaling pathway
cellular response to DNA damage stimulus
mitotic cell cyclecheckpoint
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xact
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Mutated or Amplified
Mutated or Deleted
Size by:
Average (Mutation Count)
≥ 159.00
≤ 3.00
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Figure 8. Hierarchical clustering of vemurafenib EC50 values across all cell lines to the equivalent values for agents in the OncoPanel reference database reveals that the BRAF inhibitor vemurafenib clusters most closely with another BRAF inhibitor, PLX4720. Top row = target protein name, bottom row = test agent name.
Figure 9. Bliss excess based on combination testing for multiple cell lines treated with the same combination of agents. This excess is converted into the Bliss sum, which shows whether the combination is antagonistic (negative) or synergistic (positive) for all concentration combinations, per individual cell line.
BENCHMARK TEST AGENTS TO INFORM ON CLINICAL POTENTIAL
• Gain understanding of biological impact and clinical potential, from small molecules to biologics
• Perform competitive benchmarking to over 60 standard-of-care agents and reference tools
ADDRESS EFFICACY AND RESISTANCE CHALLENGES WITH DRUG COMBINATION STRATEGIES
• OncoPanel™ offers 9x9 combination matrix testing across subpanels, individual OncoPanel cell lines, or custom cell lines
• Analysis includes calculation of combination indices, individual test agent dose responses, and determination of excess over Bliss independence
ENHANCE YOUR PRECLINICAL KNOWLEDGE BASE: INSIGHTS ON EFFICACY, MECHANISM OF ACTION, AND BIOMARKER IMPACT
Bliss Excess
Test
Age
nt C
once
ntra
tion
(μM
)
1.56E-004
3.13E-004
6.25E-004
1.25E-003
5.00E-003
2.50E-003
1.00E-002
2.00E-002
4.00E-002
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CONTACT US
Work with our technical and scientific experts to find out how OncoPanel™ Screening and Profiling Services can accelerate your drug discovery and development efforts. Our phenotypic experts are ready to assist in designing an approach to meet your program needs and quickly advance your projects. OncoPanel may be customized, and used for therapeutic areas outside oncology.
Get in touch at [email protected]
Eurofins Discovery Phenotypic Services—easing your path on the journey from concept to clinic.Contact us at: [email protected] or visit us on the web at: eurofinsdiscoveryservices.com/phenotypic
PARTIAL OncoPanel CATALOG INFORMATION
Catalog Item DescriptionPSOP0001 OncoPanel, Full 3D Spheroid Panel, with 2D Control, Cell Viability OncoPanel 3D with 2D Control
PSOP0002 OncoPanel, Full 3D Spheroid Panel, without 2D Control, Cell Viability OncoPanel 3D no 2D Control
PSOP0010 OncoPanel, Full Panel: High Content Imaging Cell Proliferation Assay, 10-day long-term 10-day singleplex
PSOP0011 OncoPanel, Full Panel: High Content Imaging Cell Proliferation Assay, 3-day 3-day singleplex
PSOP0012 OncoPanel, Full Panel: High Content Imaging Cell Proliferation Assay, 5-day 5-day singleplex
PSOP0013 OncoPanel, Full Panel: Multi-Parameter High Content Profiling Assay, 10-day long-term 10-day multiplex
PSOP0014 OncoPanel, Full Panel: Multi-Parameter High Content Profiling Assay, 3-day 3-day multiplex
PSOP0015 OncoPanel, Full Panel: Multi-Parameter High Content Profiling Assay, 5-day 5-day multiplex
PSOP0079 Cell Viability in Full OncoPanel: Luminescence Assay, 10-day long-term 10-day cell viability
PSOP0080 Cell Viability in Full OncoPanel: Luminescence Assay, 5-day 5-day cell viability
PSOP0081 Cell Viability in Full OncoPanel: Luminescence Assay, 3-day 3-day cell viability
PSOP0082 OncoPanel Genomics Analysis, Add-On or Custom OncoPanel Genomics Analysis
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PHARMA PHARMA PHARMA PHARMA PHARMA DISCOVERY DISCOVERY DISCOVERY DISCOVERY EXPERTISE EXPERTISE EXPERTISE EXPERTISE PHARMA PHARMA PHARMA PHARMA PHARMA DISCOVERY DISCOVERY DISCOVERY DISCOVERY
PHARMA PHARMA PHARMA PHARMA PHARMA DISCOVERY DISCOVERY DISCOVERY DISCOVERY EXPERTISE EXPERTISE EXPERTISE EXPERTISE PHARMA PHARMA PHARMA PHARMA PHARMA DISCOVERY DISCOVERY DISCOVERY DISCOVERY
PHARMA PHARMA PHARMA PHARMA PHARMA DISCOVERY DISCOVERY DISCOVERY DISCOVERY EXPERTISE EXPERTISE EXPERTISE EXPERTISE PHARMA PHARMA PHARMA PHARMA PHARMA DISCOVERY DISCOVERY DISCOVERY DISCOVERY
PHARMA PHARMA PHARMA PHARMA PHARMA DISCOVERY DISCOVERY DISCOVERY DISCOVERY EXPERTISE EXPERTISE EXPERTISE EXPERTISE PHARMA PHARMA PHARMA PHARMA PHARMA DISCOVERY DISCOVERY DISCOVERY DISCOVERY
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