Kirsi Ketola

We study the molecular mechanisms of cancer cell plasticity and prostate cancer treatment resistance including neuroendocrine transdifferentiation and cellular neuroplasticity programs in prostate cancer. We aim at identifying novel therapeutic targets and biomarkers for neuroendocrine prostate cancer and ways to bring treatment resistant prostate cancer cells back to antiandrogen therapy sensitive state. We employ several genome-wide and cellular imaging methods such as RNA-seq, ATAC-seq, ChIP-seq and live-cell high-content and -throughput imaging and drug screening to understand and target through precision medicine approaches the cellular plasticity stages and epigenetic reprogramming in cancer treatment resistance. We also utilize patient-derived organoids of prostate and neuroendocrine prostate cancer patients as well as patient blood samples on different treatment stages to identify and validate our findings. Our recent identified novel players highly overexpressed after antiandrogen therapy include neuroplasticity protein DPYSL5, which regulates antiandrogen enzalutamide resistance, chromatin reprogramming and neuronal cell phenotype in prostate cancer, Fanconi anemia pathway and FANCI which plays a role in carboplatin resistance in prostate cancer as well as a stem cell transcription factor which turns on cancer stem cell and resistance program in androgen-independent prostate cancer. By inhibiting these cellular plasticity programs we believe we can target the development of aggressive forms of cancer.

Find Ketola Lab pages: https://uefconnect.uef.fi/en/group/cancer-cell-plasticity-ketola-lab/