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Second Generation Diagnostics: iMALDI-based Assays for Protein Activity to Improve Patient Selection for Therapeutic Akt Inhibitors in Cancer Treatment

Genomic Applications Partnership Program
GAPP Round: 
Genome Centre(s):
Génome Québec, Genome British Columbia
Project Leader(s):
Christoph Borchers (University of Victoria), Gerald Batist (McGill University)
Receptor Leader(s):
Paul Elvin (AstraZeneca)
Fiscal Year Project Launched: 
Project Description: 

Cancer, research is discovering, is not the monolithic disease it was once thought to be. In fact, most cancer types have many sub-types, each with its own distinct molecular signature. In some instances this molecular signature determines whether or not a particular drug therapy will be effective. 

AZD5363 is an anti-cancer drug in clinical development by AstraZeneca, which has been shown to stop tumour cell growth by inhibiting a protein called Akt. AstraZeneca and the clinical community want to be able to  understand more accurately which patients are likely to respond best to this drug and is conducting exploratory research on tumour tissue as well as blood to address this challenge.  New technology developed by Dr. Christoph Borchers, called immunoMALDI (iMALDI), uses antibodies and mass spectrometry to monitor for multiple forms of the Akt protein in a single assay. The clinical trials ongoing with AZD5363 provide the opportunity to validate iMALDI and proteomics in samples from patients with mutations in the PI3-kinase/Akt pathway and to test the concordance of iMALDI with other types of mutation testing for molecular signatures.

If iMALDI demonstrates clinical utility, the test may be used to identify patients with specific types of protein and pathway activation to enrich clinical trials with those patients most likely to benefit from the trial treatment, and to determine who will respond best to Akt inhibitors once approved. If successful, this project may lead to the development of a diagnostic test that will be commercialized by Victoria-based MRM Proteomics Inc.

The ability to use proteomic tests such as iMALDI to identify those most likely to respond to particular treatments will also help Canada attract millions of dollars in biopharma investment to further develop protein-based biomarkers.