Manipulating drivers of transcriptional heterogeneity

Breast cancer is the most common cancer among women, with more than 2 million new cases each year worldwide including about 7,000 in Austria. It is also one of the deadliest cancers, causing over 600,000 deaths every year. About two-thirds of breast cancers are sensitive to hormones and can be treated with hormone-blocking therapies. These treatments often work well at first, but for about 1 in 5 women, the tumor returns within 10 years and becomes much harder to treat. These returning cancers are often resistant to many types of therapy and can spread to important organs. Our research aims to find new ways to prevent or delay this deadly relapse. To do this, we will study how cancer cells slowly adapt to treatment and look for ways to limit their ability to evolve ultimately stopping them before they become resistant. While previous research mainly focused on changes to the DNA of cancer cells, we will investigate more subtle changes that help cells survive treatment. These changes involve factors that affect the activity of the epigenome the layer of molecular signals that control how genes are turned on or off. Such changes may be more common than genetic mutations specifically linked to therapy resistance, and they can potentially be reversed with drug treatments. We will use cutting-edge laboratory tools including gene editing and single-cell genomics techniques along with computer simulations and AI-powered classifiers, to reconstruct the epigenetic networks that drive how cancer cells respond to treatment and gradually develop resistance. We will also test our findings in tumor samples that preserve the full biological context found in the human body. This work could lead to new treatments that improve the life expectancy of thousands of breast cancer patients each year. It may also help scientists understand how many types of cancer develop resistance to treatment not just breast cancer.