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Functional characterization of novel non-coding RNA transcripts in bladder cancer

Adrian Gunaratne

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Canadian Institutes of Health Research (CIHR)
Bladder cancer is one of the most common types of cancer in Canada. Various subtypes of bladder cancer respond differently to treatment, and recurrences are frequently observed. Under the microscope, many bladder cancers that are invasive look the same as ones that are more benign, even though may have very different genetic characteristics. There are currently no targeted therapies for bladder cancer, and the primary treatment is to surgically remove the bladder, an operation which significantly impacts the patient's quality of life, and is often times unnecessary. Thus, it would be imperative to know whether specific cancers could be targeted for death without bladder removal. Working with world leading clinicians and scientists, we have used cutting edge genetic tools called RNAseq and DyNeMo to analyze specific genetic characteristics of aggressive types of bladder cancer from frozen patient samples. Preliminary results point to very specific cell signalling pathways which can drive the migration and growth of bladder tumours. We also identified very unique intracellular biological molecules called 'enhancer RNAs' that can be potential candidates for targeted therapy as they are specific to each type of cancer. Initial results aimed at depleting these molecules in bladder cancer cell lines have yielded encouraging results, highlighted by an increase in cancer cell death. Continued work will aim to characterize the signalling pathways that make the bladder cancers more invasive and also to characterize the enhancer RNAs for the specific and targeted treatment of various bladder cancers. Ultimately, we hope that using our tools we will create a diagnostic genetic signature of aggressive bladder cancers, so that a patient's initial surgical sample can be used in a test in the clinic to determine whether a patient requires surgery or not, and whether they may be a candidate for a targeted treatment.

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