A multi-parametric liquid biopsy approach to explore therapeutic resistance in patients with Triple-Negative Breast Cancer

Liquid biopsies that focus on circulating tumour DNA (ctDNA) and circulating tumour cells (CTCs) are being investigated for detection and monitoring of cancer. Although CTCs reflect metastatic disease, they are not routinely investigated in the clinic due to the cost and difficulty with current workflows. My proposed activities shall use a novel simple semi-automated workflow (that I recently developed and validated with cell line models) to recover CTCs in patients with triple negative breast cancer (TNBC) with the goal of determining their phenotype at the time of metastatic disease progression. While new treatments like chemo-immunotherapy have improved outcomes, development of drug resistance remains a significant issue in TNBC. Reliable biomarkers for prognosis and treatment monitoring are lacking, hence a clear unmet need. My key project goals are to develop my collaborative networks and expertise in CTC workflows, omics, bioinformatics and biostatistics to address critical gaps in current liquid biopsy analyses by focusing on multi-parametric assessment in TNBC. By investigating CTC transcriptional signatures associated with treatment resistance and integrating them with specific DNA methylation signatures in cfDNA. I aim to identify novel biomarkers of progression for chemo-immunotherapy, to support novel therapeutic management approaches for TNBC.