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Oncology

WuXi Oncology is a part of the integrated solution. We work diligently with our partners to advance cancer biology towards effective therapeutic intervention by offering a comprehensive oncology platform including patient-derived xenograft (PDX) models with in-depth genomic characterization.

Scope

Biochemical assays

  • Enzyme assays, compound profiling, and screening
    • Biochemical assays for purified enzymes
      • kinase, methyltransferase/demethylase, dehydrogenase, polymerase and others
      • capability of assay transfer and development
    • Potency (IC50 & Ki) measurement for enzyme inhibitors
    • Kinase selectivity panel: >80 kinases and expanding
    • Mechanism of action studies for enzyme inhibitors
      • mechanisms of inhibition
      • reversibility
      • on/off-rate determinations for enzyme-inhibitor interactions
    • HTS screening capability with fast turnaround and high quality

Oncology cell based mechanistic and phenotypic assays

  • ELISA, Alphascreen, in-cell Western, etc.
  • Viability/proliferation assays: CellTiter-Glo, MTS, BrdU ELISA, etc.
  • Apoptosis assays: Apo-One, caspase-Glo, cell death ELISA, sub-G1, etc.
  • Other assays validated: cell cycle, soft agar, cell mobility, angiogenesis, etc.
  • Cell panel screening including combinational screening
  • Cell-based MOA studies

Colony formation/soft agar assay

Target validation

  • Target gene over-expression

    • Transient transfection or lentiviral system
    • Establishment of stable cell lines
  • Target gene silencing

    • Lentiviral shRNA
    • siRNA transfection
  • Readout

    • Mechanistic readout
    • Target relevant phenotypic assays

Cancer Stem Cell (CSC) platform:

CSCs are propagated from primary tumor cells freshly isolated from PDX tumor tissues. These cells are highly tumorigenic and drug resistant, providing a CSC-relevant model for drug test

Cell line-Derived Xenograft (CDX) models

  • Over 100 validated subcutaneous xenograft models covering 19 different cancers: Bladder (3), Brain (1), Breast (7), Cervical (1), Colorectal (14), Duodenal (1), Gastric (2), Head & Neck (2), Hematopoietic (20), Liver (8), Lung (16), Mastocytoma (1), Melanoma (4), Ovary (4), Pancreas (4), Prostate (2), Renal (4), Sarcoma (5), and Skin (1) cancers
  • Twenty-seven luciferase-tagged cell lines for orthotopic and metastatic studies using an onsite bioluminescent imaging system, with available customer tagging of additional cell lines
  • Complete list of cell lines available on request

Syngeneic models

Mouse cancer cell lines validated in matching mouse strains

Cell Line Cancer Type Strain of Origin
Hepa1-6 mouse (C57) liver cancer C57L
EL4 mouse T cell lymphoma C57BL/6N
4T1-luc mouse mammary adenocarcinoma BALB/cfC4H
MBT2 mouse bladder C3H
LL/2(LLc1) mouse lewis lung mouse
P815 mouse lymphoblast-like mastocytoma DBA/2
4T1 mouse mammary adenocarcinoma BALB/cfC3H
RENCA mouse renal carcinoma Balb/cCr
A20 mouse reticulum cell (B lymphocye) BALB/cAnN
EL4 mouse T cell lymphoma C57BL/6N
B16-F10 melanoma C57BL/6J
Colon-26 colorectal cancer BALB/c
4T1-luc mouse mammary adenocarcinoma BALB/cfC4H
EL4-luc2 mouse T cell lymphoma C57BL/7N
B16-F10-luc-G5 Luciferase-positive melanoma C57BL/6J

Genetically-characterized Patient-Derived Xenograft (PDX) tumor models

Patient-derived xenograft (PDX) tumor models offer clinically relevant models for drug discovery. PDX models are established in immunodeficient mice by implanting surgically resected patient tissues. Xenograft tissues can be serially passaged, cyropreserved and revived. Our studies show that the histology of PDX tissues recapitulated the features of the original samples and maintained the heterogeneity of human tumors. PDX tumor tissues retained the global gene-expression patterns of patient samples. Whole exome sequencing revealed a wide variety of SNPs in PDX models, including BRAFV600E, EGFRL858R, and JAK1S703I mutations. Analysis of copy number variations found amplification of a number of genes, including MET, AKT2, AKT3, and mTOR. Cancer stem cell (CSC) lines have been continually derived from PDX tissues. Therefore, our well-characterized PDX models provide an excellent platform for targeted drug test, CSC research, biomarker discovery and translational research (2012 AACR abstract #2351; 2013 AACR abstract submitted).

  • More than 400 PDX tumor models available
    • Lung
    • Stomach
    • Liver
    • Colon
    • Esophagus
    • Pancreas
    • Kidney
    • Head & neck
    • Cholangiocarcinoma
    • Liposarcoma
    • Uterus
  • Comprehensive clinical information
  • Molecular characterization of PDX models
    • Whole exome sequencing (100X)
    • Gene expression
    • Copy number variation
  • Drug test in primary tumor cells isolated from PDX tissues
  • Predictive biomarkers identified
    • Mutations: BRAFV600E, EGFRL858R, JAK1S703I, PTEN-deficient
    • Fusion genes: ALK fusion
    • Gene amplification: MET, AKT2, AKT3, mTOR, and more

Genetically-characterized PDX tumor models facilitate target therapy: In vivo efficacy study in a non-small cell lung cancer PDX model harboring EGFRL858R mutation

Combination of radiation and chemotherapy

Human tissue bank

More than 1,500 tumor samples collected from Chinese patients are cyropreserved and processed as FFPE blocks. Half of them have normal adjacent tissues. Comprehensive clinical information is available.

Tumor Normal adjacent

Biomarker discovery and translational research

Characterization of oncology models and patient samples for improved predictability of therapy and prognosis. Supported by WuXi Genomics Center and its dedicated bioinformatics team, WuXi Oncology aims to smooth the transition of your discovery programs into clinic

  • Next generation sequencing services
    • Whole genome sequencing
    • Exome sequencing
    • Target deep sequencing
    • DNA methylation sequencing
  • Microarray services
    • Gene expression
    • Copy number/cytogenetics
    • GWAS/genotyping

In vivo target validation: Genetically Engineered Mouse (GEM)

  • Targeting vector design and BAC acquisition
  • Construction of targeting vectors
  • Transfection and selection of ES clones with correct targeting
  • Removal of the neo-R cassette with transient Cre expression
  • Microinjection of ES clones to pseudo-pregnant mice
  • Breeding of chimera for germ-line transmission of targeted mutation
  • Identifying Founder Mice For Development and Oncology Analysis