Patients with breast and ovarian cancers require a reliable genetic test to assess their eligibility for targeted drug therapies. However, current tests are predominantly designed to detect only germline mutations and not epigenetic alterations, such as DNA hypermethylation, which are also predictive biomarkers for drug sensitivity.
To overcome this, we aim to combine two commercially available genetic and epigenetic tests into a novel, single-tube assay which identifies both, genetic and epigenetic causes of aberrant gene functions in cancer cells. The new multi-omic test will be cost-effective, sensitive and more convenient for the patient as a single sample feeds both assays. Consequently, this novel test will be validated in the clinical setting to select for patients that are likely to respond to targeted drug therapies.
Furthermore, it has been recently discovered that determining the copy number assessment of methylated and unmethylated alleles is critical to accurately determining the level of gene silencing, and thereby, predict a drug response. To achieve this, an independent laboratory-use assay will be developed to determine if the target genes are at complete or partial methylation. The assay will employ spatial techniques to acquire information such as tumour heterogeneity and tumour purity.
One or both of these tests will then be utilised to screen patient samples to perform targeted drug assessments. Specifically, 3D tissue models, known as organoids, derived from breast and ovarian cancer patients (PDOs) will be developed in the laboratory to study sensitivity or resistance to targeted therapies based on their genetic and epigenetic profile.
Altogether, a combination of the novel tests and 3D models will help us take personalised treatment options to the next level and improve patient cohort stratification based on their predictive response to drug therapies.