Drug Resistance
The growing demand for Horizon’s X-MAN cell models has been driven by Horizon co-founder, Professor Bardelli’s studies on patient drug resistance, published in the Journal of Cancer Research (March 2007) and the Journal of Clinical Oncology (October 2008).
These studies retrospectively analyzed tissue samples from clinical trials on the novel ‘EGFR’ targeting colorectal cancer drugs; Erbitux and Vectibix (marketed by Imclone/BMS and Amgen, respectively) and found that the majority of patients that carry a secondary mutant gene (KRAS and BRAF) are resistant to these drugs (in a combined total of 52% of patients trialled). These data were subsequently confirmed in prospective trials performed by the pharmaceutical companies developing these drugs and the European Medicines Agency (EMEA) has now mandated the compulsory testing of all colon cancer patients for these resistance genes before any EGFR-targeted drugs can be prescribed. The American Society of Clinical Oncologists (ASCO) is similarly petitioning for these guidelines to be adopted in the U.S.
These findings/rulings have limited the market size, profitability and patient efficacy of these drugs at a time when hundreds of millions of dollars have been spent on their development. However, if it can be determined that a rational combination of drugs to use in genetically characterised resistant patients, the market size for your drug can soon expand dramatically.
Patient-relevant X-MAN cancer cell-models can predict such genetic-based clinical outcomes for single and combinatorial treatment regimens; guiding focussed project development; clinical trial design and the recruitment and marketing/co-marketing of more effective therapeutic regimens.
X-MAN Discovery 2 (double mutation knock-in) cell-lines model the precise effects of secondary mutations on primary patient genotypes known to respond to a clinical EGFR active drug (Gefitinib).
Click on the image to enlarge.
ll
Additional 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
- Bianchi et al, Cancer Research, 2009
- Di Nicolantonio et al, Journal of Clinical Oncology, 2008
- Benvenuti et al, Cancer Research, 2007
- Horizon Discovery Ltd. Technical Presentation (Download)
