News & Publications
Congratulations to Damian Lai and Dr. Xiaoyan Jiang’s team, who received 2nd place prize in BCCRC’s Outstanding Trainee Publications 2018 competition
Article: Lai D, Chen M, Su J, Liu X, Rothe K, Hu K, Forrest DL, Eaves CJ, Morin GB & Jiang X. PP2A inhibition sensitizes cancer stem cells to ABL tyrosine kinase inhibitors in BCR-ABL+ human leukemia. Sci Transl Med (Sci Transl Med, IF:16.796) 10: 427, 2018. View PubMed link
The first author of this paper, Damian Lai, was a MSc student under Dr. Jiang’s supervision in the Experimental Medicine Program, UBC. He is now a Medical School student at Georgetown University in Washington.
In this study, an advanced drug/proliferation screen was performed, which uncovered a pro-survival role for protein phosphatase 2A (PP2A) in TKI-insensitive leukemic stem cells, regulated by an AHI-1-mediated PP2A-β-catenin-BCR-ABL-JAK2 complex. Damian and his co-authors demonstrated that genetic and pharmacological inhibition of PP2A, with selective LB100 and LB102 inhibitors (provided by Lixte Biotechnology Holdings), significantly impairs survival of TKI-nonresponder cells and sensitizes them to TKIs in vitro and in pre-clinical xenotransplant models. He also provided novel insights that the combination treatment leads to protein degradation of several key proteins. A Phase I clinical trial of LB100 for the treatment of relapsed solid tumors has been successfully completed without safety issues (NCT01837667), which opens a promising avenue for combination cancer therapies. The manuscript was published in Sci Transl Med in 2018. This article was highlighted in MedPak on Feb 8, 2018 and in a press release by Globe Newswire on Feb 9. It was featured in Cancer Stem Cell News, Science in the City and PHSA/BCCA News, with links on twitter and Linkedin channels, etc.