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Publications of the Week

Targeting BCR-ABL+ Stem/Progenitor Cells and BCR-ABL-T315I Mutant Cells by Effective Inhibition of the BCR-ABL-Tyr177-GRB2 Complex

By June 26, 2017No Comments

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 This week we profile a recent publication in Oncotarget from the laboratory of Dr. Xiaoyan Jiang (centre) at the Terry Fox Laboratories.

Can you provide a brief overview of your lab’s current research focus?

The focus of our translational leukemia research is to identify key molecules and pathways that will lead to new, rationally designed, more effective, less toxic, personalized molecularly targeted therapies. In particular, we are extremely interested in developing mechanism-based combination therapeutic strategies that can directly target drug-insensitive blood cancer stem cells, leading to curative therapies for human leukemia.

What is the significance of the findings in this publication?

We demonstrated that newly developed, selective SNG inhibitors, which target specific oncogene mutations and cancer survival pathways, in combination with current standard treatment drugs (tyrosine kinase inhibitors) are significantly more effective in eliminating drug-insensitive blood cancer stem cells and mutant cells obtained from chronic myeloid leukemia (CML) patients, while not being toxic to healthy bone marrow cells.  This new combination therapy may lead to more effective disease eradication, especially in patients at high risk of drug resistance and disease progression.

What are the next steps for this research?

SNG inhibitor phase I/II clinical trials in China have recently been completed, with encouraging results for patients with advanced solid tumors (NCT01278810, NCT01972672, NCT02496949). A phase III trial will be initiated soon.  A potential clinical trial for CML treatment has been discussed with our collaborators at Shenogen Pharma Group Ltd, based on our significant findings.

This project was supported by:

This work was supported by the Canadian Institutes of Health Research and research funding from Shenogen Pharma Group Ltd and in part by the Leukemia & Lymphoma Society of Canada, the Cancer Research Society and the Canadian Cancer Society.

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