Oncology X-Man Cell Lines (in partnership with Horizon Discovery)

The X-Man^TM  'Mutant and Normal' panel of human 'isogenic' cancer cell-lines are pairs of cell lines; one of which has a defined disease causing mutation, just as occurs in a cancer patient, and the other a perfectly matched normal genetic background; to provide an ideal reference set to understand a 'genes' role in disease biology.



These 'patient-relevant' cell-based tools  will allow drug discovery researchers to quickly define a drug candidate's specific activity and likely patient responsiveness or resistance prior to entering clinical trials using a high-throughput assay.

The inclusion of X-Man cell-line pairs in the discovery process enables scientists to better understand the mechanism of action of lead compounds, directly identify patient-relevant compounds from large compound libraries, re-profile existing drugs for new therapeutic indications, assess the efficacy of a drug combinations, and identify potential side effects earlier in the discovery process.

Broad Applications in Drug Discovery

•  - Identify & validate patient-relevant targets.
•  - Identify selective compunds earlier.
•  - Match drug to responsive patient populations.
•  - Design shorter, patient-relevant clinical trials.
•  - Find diagnostic and predictive biomarkers.
•  - Determine 'on' v's 'off' target effects.

CDAS Offering
CDAS in partnership with Horizon Discovery offers a wide range of product and services to give industry and academic scientists access to the X-Man cell lines:

 - Cell-Line Licensing: For Evaluation, R&D, Screening, Clinical-Trial Design
 - Custom Engineering: Design your own X-Man cancer models
 - Compound Screening and Profiling: Short-cut activity acreens, patient selectivity profiling
 - Strategic Partnerships: Custom programs combining CDAS oncology service platforms.

Available Cell Lines
CDAS offers Compound Screening and Profiling Services on the following X-Man Lines.

Cancer Gene	Parent Cell	Notes
P13Ka (H1047R)	Normal Breast Epithelium	Activity kinase domain mutation
P13Ka (E545K)	SW48 Colon Cancer Cells	Activating hinge domain mutation (Parental cells 'wild-type' for P13Ka)
EGFR (del E746-A750)	Normal Breast Epithelium	Activating mutation highly responsive to Gefitinib and Eriotinib
K-Ras (G13D)	Normal Breast Epithelium & SW48 Colon Cancer Cells	Activating mutation destroying GTPase activity leading to constitutive Ras-signaling
B-Raf (V600E)	Normal Breast Epithelium & SW48 Colon Cancer Cells	Activating kinase domain mutation
P13Ka (H1047R) & EGFR (del E746-A750)	Normal Breast Epithelium	Double knock-in of two cancer genes
New for 2008
•  KO of PTEN in normal breast and prostate epithelia
•  KI of p53 in normal breast and prostate epithelia
•  KI of B-catenin in normal breast and prostate epithelia