Drug Resistance
Horizon founders have been at the forefront of proving that the clinical outcomes of colorectal cancer patients in Phase III trials ARE directly related to their genetic profile. Bardelli et al have show that patients co-harborng K-Ras and B-RAF mutations are resistant to treatment of the EGFR drugs Vectabix (Amgen) and Imclone (Erbitux).
These findings limit the market size, profitability and patient efficacy of such drugs at a time when $250M to $500M has been spent on the drugs development.
Patient-relevant cancer cell-models can predict these genetic-based clinical outcomes before even $10M is spent on a drug development, and which can guide the focus of project development; clinical trial design and recruitment and marketing/co-marketing of more effective therapeutic regimens.
X-MAN Discovery 2 (double mutation knock-in) cell-lines model the effects on secondary mutations on primary patient genotypes known to respond to a clinical EGFR active drug (Gefitinib)
Figure 1: Here we show that B-Raf or PI3K secondary patient mutations completely reverses sensiitivity to Gefitinib – this kind of mutational resistance is now being seen in numerous Phase III clinical studies of cancer drugs e.g., Bardelli et al., Cancer Research, March 2008 and; JCO, November 2008.This 3000-fold assay window can be used for identifying drugs that reverse resistance and/or the re-positioning of existing drugs for other indications as targeted combination cancer treatments;
Relevant data-sets are available for each application and can be shared under confidential disclosure agreement. Please write to info@horizondiscovery.com for details
Horizon Offering
- Horizon Discovery has a wide range of isogenic models available for immediate licensing or purchasing (Learn more) and; can also develop custom isogenic models or screen drug candidates against your specific gene target (Learn more)
References
- Bardelli et al, Cancer Research, March 2007
- Bardelli et al, JCO, November 2008
- Howes et al, Horizon Discovery, Unpublished, 2008
- Horizon Discovery Ltd. Technical Presentation (Download (6.95MB))