"Primary localized prostate tumors usually have a good prognosis. However, some of them can progress to malignant, castration-resistant prostate cancer, which no longer respond to standard treatment, and which may spread into bones and other tissues", Eerola says.
"Based on the data presented in the thesis, expression of all three PIM kinase family members is enhanced in prostate cancer compared to benign prostate tissue, similar to two other proteins associated with this type of cancer, the MYC and ERG transcription factors. Moreover, expression of PIM kinases increases along with worse prognosis of prostate cancer", Eerola explains.
In the thesis, mechanisms of action as well as target proteins for PIM kinases were also investigated. Via phosphorylation PIM kinases were observed to regulate activities of proteins such the CXCR4 chemokine receptor and the NFATC1 transcription factor, which in turn increased the motility of prostate cancer cells.
In addition, the effects of one PIM-targeting compound, DHPCC-9 was tested. This inhibitor was shown successfully prevent tumorigenic growth, angiogenesis and metastatic spread of prostate cancer cells inoculated into the prostates of mice. Similar PIM-selective inhibitors have already been in clinical trials, but so far none of them are commercially available.
"As not only PIM kinases, but also MYC and ERG proteins affect prostate cancer progression, combinational therapies simultaneously targeting multiple proteins may improve the prospects of patients as compared to monotherapies", Eerola says.
MSc Sini Eerola was born in Kangasala and graduated from High school of Kangasala in year 2005. Her academic degree was obtained from the University of Turku, Department of Biology in year 2013. Since then she has been working as a doctoral candidate, first in the University of Turku and later in the Tampere University in the Faculty of Medicine and Health Sciences.
The doctoral dissertation of MSc Sini Eerola in the field of Cancer Genetics entitled The role of PIM kinases in prostate cancer – promoting and inhibiting factors will be publicly examined in the Faculty of Medical and Health Sciences in the Tampere University at 12 AM on Friday 11th of Mach 2022 in Arvo building auditorium F115, address: Arvo Ylpön katu 34. The Opponent will be Professor Juha Klefström from the University of Helsinki. The Custos will be Professor Tapio Visakorpi from the Faculty of Medical and Health Sciences.
The dissertation is available online at
https://urn.fi/URN:ISBN:978-952-03-2316-5
Photo: Auri Kohola