Project

Ex Vivo Image-based Drug Profiling for Discovery and Personalization of Myelofibrosis Treatments

Short Summary

Patients suffering from myelofibrosis, a chronic blood disease, currently have very limited treatment options. A high need for both new therapies and better personalization of current therapies exist, yet despite improved molecular knowledge regarding the disease, mechanisms underlying response to therapy remain unknown. Pharmacoscopy is an image-based drug profiling technology that enables discovery of drug efficacy in a patient, by measuring the activity in the patient’s own blood. Furthermore, to gain an improved understanding of the molecular mechanisms that determine the response to a drug, we will correlate the pharmacoscopy drug profiling results to sample-matched subpopulation proteomics. In this iDoc, we aim at using pharmacoscopy in the clinical myelofibrosis setting, to improve and personalize treatment of this disease.

Goals

This iDoc project aims at discovering and personalizing myelofibrosis treatments. By employment of the pharmacoscopy technology, therapies can be found and characterized that lead to targeted killing of diseased cells while sparing healthy blood cells. Using pharmacoscopy, we aim at a) discovery of new treatment modalities to be administered in the clinics and b) personalization of both current and new treatments by characterizing patterns and underlying mechanisms of sensitivity and resistance within myelofibrosis patients.

Significance

Currently, there is a very limited treatment potential for myelofibrosis patients. Available therapies mostly aim at symptom reduction, given that they do not target the diseased cells over normal cells. Furthermore, response to therapy is variable, yet processes underlying either response or resistance to therapy are completely unknown. Here, we aim to improve both clinical aspects by employment of the pharmacoscopy technology on a patient cohort, thereby discovering new therapeutic options and personalizing both existing and new therapies on an individual-patient level. We furthermore will elucidate molecular signatures underlying response to therapies by correlating the proteomic landscape of our patient cohort to their respective drug responses.

Background

Myelofibrosis is a chronic disease, mostly affecting elderly people, in which normal blood production is deregulated. In absence of a potent targeted therapy to treat these patients, patients currently suffer from scarring of the bone marrow, increased spleen size, and symptoms related to the altered blood production, including easy bruising and easy bleeding. Furthermore, patients are at risk of cardiovascular events and transformation of the disease into an aggressive leukemia. Currently, the most targeted therapy for myelofibrosis is Ruxolitinib, a targeted JAK inhibitor. Despite that this drug reduces symptoms and extends life span, not every patient responds to it, resistance can develop during treatment, and most importantly: it does not target the diseased cells. A method to find targeted therapies for blood diseases is pharmacoscopy. In short, the method enables screening of a drug panel in a patient’s own blood, thereby including both the diseased and healthy cells present in a patient. Response to treatments is determined using high-throughput automated imaging, enabling distinction between responses on healthy and diseased cells. Selecting drugs that selectively kill diseased cells while sparing healthy cells present in a patient, has proven to allow for an improved prediction of response of a patient to therapies.

iDoc

Consortium

Status

Completed

2nd Call, iDoc