Poly ADP Ribose Polymerase inhibitors (PARPi) are a class of drugs that serve as targeted therapy for cancers with Homologous Recombination DNA Repair Deficiency (HRD), reliant on non-homologous end joining (NHEJ). HRD can occur by inactivation of related genes such as BRCA through mutations or silencing. PARPi bind to the PARP enzyme, preventing its repair of single strand DNA nicks. The accumulation of DNA nicks results in double stranded DNA (dsDNA) breaks which proves lethal in cells using to repair dsDNA breaks. PARPi mediated synthetic lethality has been demonstrated durable responses in sub-population of patients with HRD. The key is identifying those patients who are likely to respond.
Epic Sciences has developed the Epic HRD Test, to identify patients with HRD from a simple peripheral blood draw through single cell imaging of individual circulating tumor cells (CTCs). Parallel high content image analysis and single cell sequencing characterized the observed morphological differences between cells sequenced with high genomic instability, a signature of HRD, vs. those with low genomic instability. Subsequently, the Epic Sciences team developed a propriety algorithm that can predict cells with high genomic instability and identifies an HRD phenotype (figure 1, as presented at ASCO 2016) based on image analysis alone.
This new test will facilitate both clinical trials and drug discovery by:
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