Browsing by Subject "doctoral Programme in Biomedicine"

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  • Casado, Julia (Helsingin yliopisto, 2021)
    Cancer continues to be a major clinical and societal challenge. Globally, the cancer burden rises every year with a new record of 18.1 million new cases and 9.6 million cancer deaths, as reported by the World Health Organization. Despite the increased financial efforts of western countries to cure this disease, it is expected that in the year 2040, over one-third of the population will be diagnosed with cancer. The gap in translating basic research into clinical benefit requires cross-disciplinary approaches to harness large data from the complex molecular systems and cellular organization within the tumor. The main obstacles in current cancer care are late detection and therapy resistance. While high-throughput and single-cell methodologies have become an advisable tool to analyze molecular profiles, their use for clinical decision-making is still missing. This thesis aims to propose efficient methodologies to connect molecular and cellular profiling research to cancer therapy outcomes. In the first and second publications, we made available software to rapidly analyze large mass cytometry data with high resolution and interaction-assisted interpretation steps for the analysis. These methods allow the rapid profiling of tumor cell populations and their association with therapy response. As part of the third project, we developed new image analysis methods to identify therapy response predictors from highly multiplexed images. We found that spatial organization within the tumor microenvironment was highly associated with DNA damage genome scarring. In the fourth study, we designed a new method to identify epigenetically reversible drug resistance mechanisms in tumor cells. The application of novel methodologies contributed to a better understanding of the roles of genomic and proteomic features in the tumor-immune microenvironment in response to modern anti-cancer therapies.