Johan Lindberg

This project was started to develop precision medicine for disseminated prostate cancer. All healthy individuals have DNA from dead cells in their blood. In patients with cancer, some of the free-floating DNA in blood comes from the cancer cells. This DNA is called circulating tumor DNA. In this project, new technology will be used to explore different uses for circulating tumor DNA, for example whether it can be used to follow treatment response and determine treatment choices. The project will study disseminated prostate cancer and all treatments used to treat this disease. The project is about using newly developed technology to identify biomarkers through analysis of circulating tumor DNA. The goal of this project is to provide oncologists with a tool to better follow and understand whether a patient is responding or not responding to a treatment by monitoring ctDNA levels in blood over time. Another goal is to improve treatment choices through analysis of circulating tumor DNA.

The lack of treatment-predictive biomarkers is an unmet clinical need in metastatic prostate cancer leading to inferior clinical outcomes, overtreatment and accelerating costs. The ProBio study (NCT03903835) is an ongoing randomized trial that builds on a novel adaptive study design and prospectively evaluates treatment predictive biomarker signatures in a large network of over 35 study centers in Europe. By using ProBio we will be able to rapidly evaluate both new and old drugs in subsets of patients with similar genomic biomarker. If successful, patients with prostate cancer will get individualized treatment based on treatment-predictive genomic biomarker signatures in the near future.To test this hypothesis, we will use a multiphase randomized study using an outcome-adaptive multi-arm biomarker-driven study design. We have the following main aims: To investigate if treatment decisions based on a biomarker signature identified by sequencing circulating tumor DNA improves progression free survival (primary endpoint)To ultimately show that the ProBio concept is a model for collaboration between academia and industry in the evaluation of new drugs in prostate cancer

Prostate cancer is the most common form of cancer in Sweden. Although survival is 92% after 5 years, prostate cancer takes the most lives of all cancer types. A challenge with prostate cancer is that many men carry a completely harmless cancer that will not cause any symptoms if left undetected. The widespread PSA testing therefore leads to unnecessary side effects and costs to society. The Stockholm3 test is a blood test based on a combination of biomarkers that was developed to meet these challenges. Combined with new technology that improves the precision of biopsy, the problems have decreased but there is room for improvement. To reduce the problems in screening for prostate cancer, new types of biomarkers are needed. One such biomarker is DNA remnants from dying cancer cells which can be purified and analyzed from plasma. Such DNA residues are called circulating tumor DNA. In this research project, circulating tumor DNA will be analyzed from patients diagnosed with prostate cancer as well as healthy individuals to investigate whether circulating tumor DNA has the potential to identify those men who need treatment and those who should not. The goal of this research is to develop a diagnostic test to improve screening for prostate cancer.