KCCG Senior Research Officer Dr Mark McCabe led the study, which was recently published in Cold Spring Harbor - Molecular Case Studies.
Dr McCabe used genomics to analyse primary and metastatic tumours from a 37-year-old woman with adrenocortical carcinoma (ACC) that had spread to her lungs.
ACC is an aggressive, rare cancer of the adrenal gland often with poor outcomes for patients, due to a lack of research into the biology of the disease. The only chemotherapy treatment option, mitotane, has a low response rate and significant side effects.
After an extensive analysis, Dr McCabe traced a series of complex changes in the tumours back to a deletion in MSH2 – a gene involved in the repair of errors in DNA.
Additional variants were found in important cancer-associated genes including TP53, PTEN and RB1.
Dr McCabe said that the multiple pathways uncovered in the study present a range of options for targeted drug therapies in some cases of ACC.
“We’re seeing a shift from treating cancer based on its tissue of origin, to a personalised medicine approach – treatment based on a tumour’s molecular profile,” Dr McCabe said. “Using genomics to build that molecular profile is the essential first step towards new targeted treatments.”
However, targeted cancer therapies can become less effective over time as a tumour develops resistance, making it extremely important to monitor the patient for recurrence. Standard biopsies to monitor tumour development can often be invasive, disfiguring or expensive.
In this study, Dr McCabe measured the DNA that is shed into the bloodstream by a tumour, known as circulating tumour DNA (ctDNA). More than 10 blood samples were analysed over two years – providing detailed information to detect cancer recurrence early.
“The liquid biopsy results confirmed the clinical signs that the patient is free of cancer,” Dr McCabe said. “It’s a truly remarkable result – long-term survival in a case like this is not unheard of, but it is very rare.”
In the event of recurrence, the molecular profile of the tumour suggests that combination immunotherapy would be the best treatment approach.
Dr McCabe is now working on a Cancer Institute NSW Career Development fellowship to develop similar genomics- and liquid biopsy-based strategies that can be applied to other understudied cancers, with the aim of improving diagnosis, prognosis and treatment.
Read more about this research in Cold Spring Harbor - Molecular Case Studies.