Personalized GU Cancer Modeling in Nanoliter Tumoroid Droplets – PHRT
Personalized GU Cancer Modeling in Nanoliter Tumoroid Droplets
Personalized medicine holds tremendous promise for the treatment of heterogeneous diseases such as cancer. The ability to test treatment approaches in representative in vitro systems that mirror the individual features of a patient’s disease, has the potential to improve treatment efficacy greatly, while avoiding unnecessary side effects. Tumoroids, small tumors grown in 3D culture, are among the most promising “patient avatars” for cancer therapy. However, their routine application in therapy design is hampered by high cost and very long assay procedures. In the course of this PHRT project, we will develop and benchmark a novel, personalized tumoroid assay that can deliver detailed susceptibility and resistance profiles for prostate and bladder cancer patients within few weeks after biopsy. Routine implementation of our assay strategy will enable oncologists to maximize the initial treatment response and minimize the development of treatment resistance.
To enable the use of patient-derived tumoroids in diagnosis and personalized therapy, we aim to develop a new kind of tumoroid assay that produces reliable results without the need of long tumoroid expansion. We will miniaturize standard drug screening assays and focus on readouts from individual organoids. To this end, we will integrate recent advances in microfluidics, tumoroid technology and imaging to deliver detailed predictions of treatment outcomes for individual patients. In close collaboration with Inselspital of Bern and UBERN, we will apply our technology to establish a personalized prostate and bladder cancer assay, which produces a detailed susceptibility profile of each tumor within the ambitious timeline of 14 days after biopsy.
Despite recent advances in the development of targeted therapeutics, correct matching of patient and therapy option is still challenging. Unexpectedly poor response to therapy and acquisition of therapy resistance makes repeated treatment cycles necessary that often come with severe side effects. Our project addresses major clinical challenges associated with these differential treatment responses by providing a functional assay to identify the most promising treatment options for each patient. Ultimately, our method could not only improve treatment outcomes for patients with prostate or bladder cancer, but could find similar application in other solid tumor types.
Adapting treatment regimens to the individual features of each tumor and patient strongly increases the chances for lasting therapeutic success. We can grow small tumor samples, (e.g. from biopsies) in culture dishes into miniature tumors that resemble the cancer of origin. Scientists around the globe have used these “tumoroids” to predict the individual susceptibilities, resistances and reactions of tumors to various forms of treatment. This could enable oncologists to test various treatment options and choose the most effective one to treat each individual patient. In fact, several co-clinical trials have already confirmed the potential value of this strategy. However, tumoroid assays are slow, hard to automate and expensive, since the initially small sample needs to be expanded until sufficient material has grown to perform standard drug testing assays. This causes long delays between biopsy and result that are not compatible with the necessary swiftness of therapeutic decisions.
Prof. Dr. Helmuth Gehart
Institute of Molecular Health Sciences, ETH Zurich
Department of Biology, ETH Zurich
Department of Biomedical Research, University of Bern and Inselspital Bern