TO 15-00023

Challenge

Population variability and narrow therapeutic indices of most chemotherapeutic drugs bring forth the risk of overdosing or undertreatment as a common threat in anti-cancer therapy. Achieving optimal tumor response without reaching systemic toxicity therefore requires a good predictive model of individual drug susceptibility. UDPGlucuronosyltransferases (UGTs) play a key role in the detoxification of activated hydrophobic drugs. Single nucleotide polymorphisms (SNPs) in their transcripts, or promotors, dramatically alter enzyme activity, leading to a rather unpredictable personal metabolic variance. While the importance of UGT1A1 activity for patient mortality has been recognized by the FDA already, analysis of other UGT1A variants now gains more importance.

Technology

The invention is directed to provide a pharmacogenetic test assay for detecting naturally occurring UGT1A7 variants. Alleles identified with this test have been shown to have an impact on phase II metabolism of well known chemotherapeutical drugs. Furthermore, some variants indicate a predisposition for  specific malignancies. Results of the assay can either be used to provide a personalized therapeutic strategy or may be applied in patient stratification during drug development and clinical trials.

Commercial Opportunity

In-licensing

Developmental Status

Detailed genotyping was done in numerous irinotecan-treated patients with metastatic colorectal cancer.

Patent Situation

Two patent families have been established based on WO002002053770A2 and WO002006027182A1. Parts of the claims have been granted in US and Japan already.

Further Reading

Lankisch et al. (2008) Gilbert's Syndrome and Irinotecan Toxicity: Combination with UDPGlucuronosyltransferase 1A7 Variants Increases Risk; Cancer Epidemiology Biomarkers & Prevention 17, 695-701.

Irinotecan metabolism. Source: Lankisch et al. (2008)

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Reference Number: TO 15-00023