NOVEL APPROACH TO CANCER TREATMENT - Isis Project No 1206

Work in the Cancer Research UK Laboratories at the Weatherall Institute of Molecular Medicine, Oxford, has uncovered an exciting new anti-cancer approach that has potential as a stand-alone therapy, and as a means of enhancing sensitivity to conventional anti-cancer treatments

Marketing Opportunity

One effective strategy to treat metastatic cancer is to induce sequence-specific silencing of target gene expression in cancer cells. The use of small interfering RNAs (siRNA) as gene silencing agents in mammalian cells is the most potent method. One important gene target with therapeutic potential in the fight against cancer is the type-1 insulin-like growth factor receptor (IGF1R). IGF1R activation induces tumour cell growth and protection from apoptosis, including that induced by conventional anti-cancer treatments. Its upregulation in tumours relative to normal tissues renders IGF1R a highly attractive anti-cancer treatment target. 

The Oxford Invention

The problem associated with IGF1R targeting is the high degree of homology between the IGF1R and the insulin receptor (IR). Because of this close homology, IGF1R kinase inhibitors and blocking antibodies can influence the function or cell surface expression of the insulin receptor, potentially inducing glucose intolerance and diabetes. The Oxford inventors used a scanning oligonucleotide array technology to design siRNAs that interact with IGF1R but not IR mRNA. This strategy has enabled identification of siRNAs that cause profound sequence-specific IGF1R gene silencing without affecting expression of the IR.

Commercialisation Opportunity

The IGF1R siRNAs have been tested successfully in vitro. Treatment of tumour cells with siRNAs blocks IGF signalling, inhibits cell survival and enhances sensitivity to cytotoxic drugs and irradiation. Work by the researchers has also shown that tumour cells remain sensitive to IGF1R gene silencing despite the presence of compensatory signaling via other growth factor receptors, or of downstream mutations causing constitutive activation of growth and survival signaling pathways. Following chemical modification to enhance stability and pharmacokinetic characteristics, the in vivo efficacy of these agents is currently being tested in human tumour xenografts.

These agents represent an exciting new anti-cancer treatment with wide applicability for patients with a variety of metastatic tumours.

Patent Status

This work is the subject of a patent application, and Isis would like to talk to companies interested in developing this approach for preclinical and clinical evaluation. Please contact the Isis Project Manager to discuss this further.

Request Further Information: Project Number 1206 Commercial Opportunity in Anti-Cancer Treatment