Prof. Leena Latonen
University of Eastern Finland
Unraveling prostate cancer drug responses and treatment resistance through multimodal proteomics
Leena Latonen
Institute of Biomedicine, Department of Medicine and Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland
Prostate cancer is one of the leading male cancers worldwide. While efficient treatment modalities exist for primary, organ-confined prostate cancer, no curative treatments currently exist for metastatic and treatment resistant forms of the disease. Genetic aberrations occurring in prostate cancer have been thoroughly described, however, these efforts have been insufficient to reveal predictive subgroups or efficient additional therapy options to support current androgen receptor (AR)-targeted therapies.
To identify molecular pathways underlying prostate cancer treatment resistance, we have performed multimodal molecular analysis of patient samples of primary and treatment resistant prostate cancer. Comparing genetic, epigenetic, transcriptomic and proteomic information from the same tumors we have found that, in addition to genetic aberrations and transcriptional changes, also significant changes in the proteomes of prostate cancer occur during formation of treatment resistance. Further, we have performed bulk and single cell proteomics of prostate cancer cells to identify activated pathways and kinetics of events in prostate cancer cell drug responses. We utilize mass spectrometry-based SWATH, Tims-TOF, and SCoPE-single cell proteomics, and we have found that, especially, multiple RNA regulatory pathways are associated with prostate cancer drug responses and resistance. We are studying multiple RNA binding proteins (RBPs) further for their roles in prostate cancer cells to identify potentially targetable factors for development of future therapeutics.
