PHARMACOSCOPY: Breaking resistance of refractory blood cancers through ex vivo automated image-based analysis of drug action

The overall aim of the PHARMACOSCOPY project is to identify effective drug interventions forpatients with treatment-resistant hematological malignancies in a personalized way. To that end, single-cell primary patient material is screened for its sensitivity to drugs with a high-throughput confocal microscope and an automated image-based analysis (single cell functional precision medicine (scFPM)). In the clinic, patients are routinely treated following standardized guidelines. Unfortunately, standards often fail leaving patients without further treatment options. Thus, the identification of individually effective (i.e. personalized) treatments against relapsed hematological malignancies is urgently needed. There are a number of studies that have utilized a range of ex-vivo drug screening methods to access functional cancer cell vulnerabilities in primary patient material with anecdotal case examples of clinical translation of findings. However, no prospective clinical evaluations have been undertaken on the feasibility and efficacy of such tests in guiding clinical treatment decisions in a difficult to treat patient population.

In this project we have conducted the first precision medicine cancer trial using a direct functional test to instruct n-of-one therapies in oncology. We have set up a multidisciplinary tumor board for therapy decisions composed of hematologists, pathologists, pharmacists, and molecular biologists. The most advanced patients with aggressive hematological cancers demonstrated a clear benefit from this approach. Our data provided evidence of the utility, efficacy, and feasibility of integrating functional drug profiling in clinical routine. We could instruct personalized treatments to a large proportion of study patients (39%; 56/143), which is a much higher percentage than in published genomics guided personalized medicine trials. Fifty-four percent of these treated patients (30/56) demonstrated a significant clinical benefit compared to their previous therapy. This study heralds the era of clinical trials built on functional precision medicine also in other medical areas and illustrates that scFPM can have a significant added value in clinical therapy guidance based on functional dependencies of each patients’ cancer.