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

  • Project Leaders: Christoph Borchers, Gaia Schiavon, Gary Kruppa, Gerald Batist, Paul Elvin
  • Institutions: McGill University
  • Budget: $554307
  • Program/Competition: Genomic Applications Partnership Program (GAPP)
  • Genome Centre(s): Genome Canada
  • Fiscal Year: 2015
  • Status: Closed

Research is discovering that cancer 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 wanted to understand more accurately which patients were likely to respond best to this drug and conducted exploratory research on tumour tissue as well as blood to address this challenge. 

Technology developed by Dr. Christoph Borchers, called immuno-MALDI (iMALDI), uses antibodies and mass spectrometry to monitor for multiple forms of the Akt protein in a single assay. An automated iMALDI-based assay for the quantification of the protein kinases Akt1 and Akt2 has been developed and translated to a clinical setting. Correlating Akt iMALDI data to clinical information and response to AZD5363 will allow assessment of the value of using the assay for selecting patients that are eligible for treatment with AKT-inhibitors. 

If iMALDI demonstrates clinical utility, the test may be used to identify patients with specific types of protein and pathway activation who are most likely to benefit from the 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.