Personalized Medicine

Advances in genomics have led to the active development of targeted therapeutics and companion diagnostics that leverage knowledge of an individual’s genetic profile to create a more personalized approach to healthcare. This makes it possible to identify those most susceptible to disease, to determine how a given patient will respond to a particular therapy, and how best to match drugs to patients based on their genetic profiles. Success, however, requires a deep understanding of which genetic variations drive key cellular events, and how these relate to an individual patient’s healthy and diseased state.

Translational genomics has become the primary tool to address this need by editing the code of the human genome in functional human cells, allowing the effects of genetic variation found in patients to be reproduced in a laboratory setting, and employed effectively within drug discovery and clinical diagnostic R&D programs.

Horizon’s scientific founders and advisors have been at the forefront of one of the first test cases for personalized medicine in the field of colorectal cancer. The COLTHERES clinical consortium (funded under the EU FP7 program) is defining the road-map for diagnosis and the development of new therapeutic regimens for cancer patients.

Horizon's precision gene-editing technology, GENESIS™, and X-MAN® cell lines lie at the center of these efforts and are driving a better understanding of basic disease biology, the design and tailoring of new treatments towards specific disease biomarkers and in the design of smaller, faster and more risk-free clinical trials by enabling pre-selection of patients most likely to respond.


One illustrative example involves Iressa® (gefitinib) and was published by Horizon co-founder Professor Alberto Bardelli in PNAS in 2008. It was found through the course of its clinical development that only 4.8% of lung cancer patients – those with specific EGFR mutations – responded to Iressa therapy. In cases like these, Horizon's approach could save many years and tens of millions of dollars in development costs. Looking retrospectively, it was demonstrated that isogenic EGFR mutant cells blinded amongst a broader panel of isogenic EGFR wild type, K-Ras, B-Raf, PI3K cells could predict the patient sub-groups who would respond or be resistant to Iressa therapy. Click here to see Application Note.

Another example is Erbitux® (cetuximab), a drug for the treatment of metastatic colon cancer. It has been shown that 40% of patients have a mutant K-Ras gene and these individuals are known to be ‘non-responders’ a fact first published in Cancer Research in 2007 also by Professor Bardelli. Currently, all patients with these mutations are being excluded from therapy. There are many different variants of mutant K-Ras however, and in a subsequent study published in JAMA in 2010, X-MAN™ lines predicted not all variants are equal. This has since been validated in the clinic, suggesting that there are patients who could benefit from Erbitux treatment who are excluded under current drug administration guidelines. Click here to see Application Note.

Paragraph explaining benefits of Biocair


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