Abstract
Cholangiocarcinoma (CCA), an aggressive cancer of the epithelial cells of the bile ducts, is unfortunately often diagnosed in the late stage, leading to limited treatment options and subsequently to poor prognosis (5-year overall survival rates of 7-20%). Late-stage, unresectable disease is typically tested for FGFR2 fusions in tissue samples. However, diagnostic tissue samples often fail to capture the heterogeneity of the disease and may be inaccessible or risky to obtain. Liquid biopsies offer a promising minimally invasive alternative. While existing molecular techniques for gene fusion detection, such as FISH, RT-qPCR, and targeted RNA sequencing, have shown efficacy, they possess limitations in terms of speed, cost, multiplexing (i.e., simultaneous detection of different markers in the same sample), technical complexity and adaptability to liquid biopsies. To address these challenges, we propose a novel enzyme-free approach utilizing a singlet oxygen-based photoelectrochemical (1O2-PEC) platform for the fusion partner-agnostic detection of FGFR2 fusions in CCA patients. This platform offers high sensitivity, rapidity, ease-of-use, possibility for multiplexing, and is cost-effective. During the project, we will develop highly specific probes, evaluate their performance and determine the minimal sample preparation for tissue and liquid biopsies as a first push towards the routine clinical practice.
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