Sarah-Jane Dawson lab

Characterising genomic and non-genomic evolution through serial tissue biopsies can be challenging due to the highly invasive nature of repeated sampling. In contrast, ctDNA can be easily obtained through minimally invasive blood sampling, repeated at regular intervals during treatment. To date, ctDNA has only been used to characterise genomic evolution and has not been utilised to study non-genetic, adaptive mechanisms of the tumour transcriptome which are equally important to understand. We are developing new tools to study transcriptional evolution through circulating tumour DNA analysis.

The majority of patients with early stage breast cancer are cured with surgery and adjuvant therapies, however, some patients will develop disease recurrence over time. There are currently no surveillance strategies routinely employed in the clinic to monitor molecular minimal residual disease (MRD) following curative treatment for breast cancer. Liquid biopsies provide a unique opportunity in this context through the analysis of ctDNA. This project aims to develop a sensitive and specific multimodality approach for ctDNA MRD detection in breast cancer to predict which patients are at highest risk of relapse.

The development of therapeutic resistance significantly limits the efficacy of many cancer treatments and represents a major problem faced in the care of cancer patients. Cancers either demonstrate de-novo resistance or develop acquired resistance to therapies through diverse processes of adaptation and selection. We are using ctDNA based approaches to monitor disease trajectories following novel therapies in breast and endometrial cancer to further our understanding of mechanisms of therapeutic response and resistance in this disease.

Diffuse large B-cell lymphoma is an aggressive and common blood cancer. A new and innovative form of cancer treatment called chimeric antigen receptor (CAR) T-cell therapy can be effective for patients with this disease, however, we cannot yet predict which patients will respond. Complex factors relating to the patient, immune system, tumour, and CAR T-cells may influence response to treatment, but the exact causes are unknown. This project aims to identify features that predict response to CAR T-cell therapy by studying blood and tissue samples from CAR T-cell recipients using new and innovative genomic techniques.

Hepatocellular carcinoma (HCC) is a leading cause of cancer deaths both globally and in Australia. Diagnosis of HCC is challenging and usually based on strict radiological criteria using multimodal contrast-enhanced imaging. In contrast to other tumour types, very few HCCs are diagnosed by liver biopsy. There is a narrow time window between detection of a liver lesion fulfilling radiological diagnostic criteria for HCC, and growth to a size where curative therapy is no longer possible. We are investigating the role of ctDNA as a minimally invasive biomarker in HCC to facilitate early detection and therapeutic monitoring in this disease.

Melanoma is the most aggressive type of skin cancer and the cause of most skin cancer deaths worldwide. Whilst most patients with early stage melanoma can be cured, some will go on to develop metastatic disease. Currently there are no biomarkers to predict which patients are at highest risk of relapse in order to determine who will be cured by surgery alone versus those requiring additional monitoring or therapy. This gap in knowledge provides a unique opportunity for the development of novel ctDNA based strategies for predictive modelling in this disease.