MD, PhD, FRCPC
- BSc, Biochemistry Honours, Queen’s University
- PhD, Dept. of Medical Biophysics, University of Toronto
- MD, University of Toronto
- FRCPC, Radiation Oncology
Non-coding RNA and tumour treatment response
MicroRNAs are a large family of short, non-coding RNA that can regulate the expression of downstream genes. Their expression patterns are changed in response to anti-cancer therapies; however, their specific role in governing response to radiotherapy is unclear. Recently, we demonstrated that miR-95 promotes tumour radiation resistance and an aggressive phenotype (Cancer Research 2013). Using in silico prediction and gene array analysis, we identified and validated sphingosine-1-phosphate phosphatase 1 (SGPP1) as a novel miR-95 target that promotes radioresistance. Treatment with FTY720, a clinically utilized small molecule inhibitor of S1P signalling, sensitized miR-95 overexpressing cells to radiation treatment. Our lab has identified and is elucidating the mechanism of several additional candidate microRNA (Oncotarget 2015) and long non-coding RNA that are involved in mediating cancer aggression and response to radiation treatment and chemotherapy.
microRNA as biomarkers to improve cancer detection and management
microRNA are detectable in patient biofluids (e.g., blood, urine, saliva), in addition to tumor, and they are inherently stable, making them excellent biomarkers. We believe that urinary microRNA are an ideal source of potential biomarkers since urine is readily obtainable and non-invasive. We believe that microRNA may also be used as predictive biomarkers to identify more aggressive forms of prostate cancer. Thus, we are determining whether testing for specific microRNAs obtained after a prostate exam, predicts for aggressive prostate cancer. If proven, this may allow the early identification of patients with aggressive prostate cancer so that appropriate treatment decisions can be made (Br J Cancer 2015).
Novel approaches to minimizing treatment-related toxicity
Most cancer patients are treated with radiotherapy, but the treatment can also damage the surrounding normal tissue. Radiotherapy side-effects diminish patients' quality of life, yet effective biological interventions for normal tissue damage are lacking. Protecting microvascular endothelial cells from the effects of irradiation is emerging as a targeted damage-reduction strategy. We have demonstrated that administration of targeted therapies for the vasculature can protect against endothelial cell perturbations and decrease the development of acute normal tissue damage in a well-tolerated manner (BMC Cancer 2014).
Hoey C, Ray J, Jeon J, Huang X, Taeb S, Ylanko J, Andrews DW, Boutros PC, Liu SK. MiRNA-106a and prostate cancer radioresistance: a novel role for LITAF in ATM regulation. Molec Oncology. 2018.
Ghiam AF, Taeb S, Huang X, Huang V, Ray J, Scarcello S, Hoey C, Jahangiri S, Fokas E, Loblaw A, Bristow RG, Vesprini D, Boutros P, Liu SK. Long non-coding RNA urothelial carcinoma associated 1 (UCA1) mediates radiation response in prostate cancer. Oncotarget. 2017 Jan 17; 8(3):4668-4689.
Mesci A, Huang X, Taeb S, Jahangiri S, Kim Y, Fokas E, Bruce J, Leong HS, Liu SK. Targeting of CCBE1 by miR-330-3p in human breast cancer promotes metastasis. Br J Cancer 116 (10): 1350, 2017.
Korpela E, Vesprini D, Liu SK. MicroRNA in radiotherapy: mirage or miRador? Br J Cancer 112:777, 2015.
Korpela E, Yohan D, Chin LC, Kim A, Huan X, Sade S, van Slyke P, Dumont DJ, Liu SK. Vasculotide, an Angiopoietin-1 mimetic, reduces acute skin ionizing radiation damage in a preclinical mouse model. BMC Cancer. 2014 Aug 26;14(1):614.
Huang X, Taeb S, Jahangiri S, Emmenegger U, Tran E, Bruce J, Mesci A, Cook E, Vesprini D, Wong CS, Bristow, RG, Liu FF, Liu SK. MicroRNA-95 mediates tumor radiation resistance by targeting sphingosine-1-phosphate phosphatase 1. Cancer Res. 2013 Dec 1;73(23):6972-86.
Associate Professor, Department of Radiation Oncology, University of Toronto|
Associate Professor, Department of Medical Biophysics, University of Toronto
Clinician-Scientist, Department of Radiation Oncology, Sunnybrook
Radiation Oncologist, Department of Radiation Oncology, Sunnybrook
Scientist, Biological Sciences – Odette Cancer Research Program, Sunnybrook Research Institute