Ovarian cancer remains one of the most lethal gynecological malignancies, with limited treatment options and poor overall survival rates. New research by scientists at the University of Tennessee Health Science Center reveals promising strategies to impede the progression of ovarian tumors by targeting deoxyhypusine synthase (DHPS), an enzyme prevalent in cancerous tissues.
Recent discoveries highlight the significant role of DHPS expression levels, which were amplified in over 10% of ovarian cancer cases studied. The findings correlate high DHPS levels with worse patient prognosis, shedding light on how manipulating this enzyme may present new avenues for therapeutic intervention.
Utilizing lentiviral CRISPR/Cas9 techniques, researchers successfully knocked out DHPS in ovarian cancer cell lines SKOV3 and OVCAR8. This knockout not only inhibited cell survival and proliferation but also suppressed the epithelial-to-mesenchymal transition (EMT)—a phenotypic shift associated with increased invasiveness and metastatic potential in cancers.
DHPS functions primarily by modifying the eukaryotic initiation factor 5A (EIF5A), which is pivotal for the translation of multiple oncogenes. Upon its inhibition, there was marked attenuation of the TGFβ signaling pathway, which is traditionally known to bolster EMT processes, indicating DHPS's central regulatory role.
Notably, when DHPS was pharmacologically inhibited using GC7, similar reductions in tumor growth and migration were observed both in vitro and in mouse models. The study culminated with significant evidence showing GC7 treatment drastically reduced the incidence of metastatic spread to organs such as the liver and kidneys.
The roles of DHPS and EIF5A present themselves as remarkable therapeutic targets. Their interplay with TGFβ signaling forms the basis for future ovarian cancer treatment modalities, potentially enhancing patient outcomes through targeted therapeutic strategies.
Overall, the research implies strong translational significance, urging the scientific community to focus on DHPS and its inhibition as promising approaches to limit the growth and spread of ovarian cancer.