LBMM awarded by a PHRT Grant

With ~19 million new diagnoses, 10 million deaths and total economic costs of 1.14 trillion US$ per year, cancer is a major burden for society. One reason for the high mortality and cost is due to the fact that every tumor responds differently to medication. Even worse, tumors rapidly change their response to drugs over time and develop resistances. This leaves patients in the highly uncomfortable position to undergo suboptimal standard therapies with unclear outcome and high mortality. What is needed is a system allowing to rapidly and economically test which drug or drug combination works best on the tumor cells of a given patient, at a given point in time.

We have previously developed a droplet microfluidic system enabling to test drug combinations directly on patient samples1. Due to the miniaturized volumes, several thousand assays can be conducted on very limited primary tumor cells e.g. from solid biopsies. Based on large translational grants in Germany (EXIST Grant 2019-2021) and Switzerland (Innosuisse Grant 2021-2023), we were able to make the technology more robust and already started pilot experiments in the clinic (with the first patient being treated according to our predictions in April 2021). However, as none of these grants funded further research and tech development, the full potential of the platform has not yet been unleashed. The aim of the current proposal is to bring second-generation (2nd-generation) platforms to the bedside, enabling a much more global view on patient’s response to drugs, facilitating even more physiological diagnostic “systems” approaches and to obtain orders of magnitude more data points per tumor sample.

In particular we will focus on five main aims:
❏ integration of global, multiplexed transcriptomic readouts (rather than single phenotypic assays, as currently used) for all tested drug combinations
❏ patient-specific pathway modelling, identification of new biomarkers and drug sensitizers
❏ use of microscopic tumor slices rather than less physiological cell suspensions
❏ upscaling and simplification of the microfluidic technology to enable routine use by non-specialized staff in the clinic or at third party diagnostic laboratories
❏ determining the clinical benefit of the 2nd-generation platform Given that our first-generation (1st-generation) microfluidic platform is already being used in a clinical context, the seamless inclusion of the above aims into translational efforts is guaranteed. This is further facilitated by a large network of clinical collaborators and industry contacts (see letters of support), with a special emphasis on strengthening the Lac Leman area.

Taken together, the development of the 2nd-generation platform is fully in line with the main goals of the PHRT initiative. In particular, it 1) enables more efficacious treatment options and patient-responsive drug selection, 2) facilitates highly affordable personalized treatment approaches, and 3) fosters close collaboration between scientists, engineers and medical clinicians.

This project will be conducted in collaboration with Prof. Julio Saez-Rodrigues, Medical Faculty, University of Heidelberg, Germany, Prof. Thorsten Cramer, RWTH Aachen University Hospital, Aachen Germany and Dr. Krisztian Homicsko, CHUV Lausanne, Switzerland.