Continuous Monitoring of Acquired Resistance to Targeted Therapy using Circulating Small RNA Sequences

HER2-positive breast cancer is the most aggressive form of cancer accounting for 20-25% of all breast cancers, with poor overall survival. HER-targeted drugs (trastuzumab, lapatinib and pertuzumab) have improved patient’s outcomes, but innate/primary and acquired resistance presents substantial clinical challenges. Acquired resistance to chemotherapeutic drugs accounts for 90% of unsuccessful treatments in advanced cancer patients resulting in relapse and metastasis. Often such resistance is detected at a much later stage and valuable time is lost in putting the patient to an alternate therapy. Acquired resistance is a result of genomic changes in the cancer cell and monitoring them is not possible using routine methods. Growing tumour often secretes small RNA (miRNA) that are stable in the blood and can be detected using PCR, leading to development of Point-of-Care (POC) diagnostic assay.

To achieve our goal, we will perform screening of circulating miRNA using blood specimens obtained from patients with acquired drug-resistance compared to drug-responsive and age-matched control. This study will significantly contribute to identifying circulating genetic markers for HER-targeted drug-resistance, uncover the drug resistance mechanism, and networks regulated by differentially expressed miRNAs.