Investigator
Hudson Institute Of Medical Research
Challenges in Implementing Comprehensive Precision Medicine Screening for Ovarian Cancer
Precision medicine has revolutionised targeted cancer treatments; however, its implementation in ovarian cancer remains challenging. Diverse tumour biology and extensive heterogeneity in ovarian cancer can limit the translatability of genetic profiling and contribute to a lack of biomarkers of treatment response. This review addresses the barriers in precision medicine for ovarian cancer, including obtaining adequate and representative tissue samples for analysis, developing functional and standardised screening methods, and navigating data infrastructure and management. Ethical concerns related to patient consent, data privacy and health equity are also explored. We highlight the socio-economic complexities for precision medicine and propose strategies to overcome these challenges with an emphasis on accessibility and education amongst patients and health professionals and the development of regulatory frameworks to support clinical integration. Interdisciplinary collaboration is essential to drive progress in precision medicine to improve disease management and ovarian cancer patient outcomes.
Hypoxia Regulates DPP4 Expression, Proteolytic Inactivation, and Shedding from Ovarian Cancer Cells
The treatment of ovarian cancer has not significantly changed in decades and it remains one of the most lethal malignancies in women. The serine protease dipeptidyl peptidase 4 (DPP4) plays key roles in metabolism and immunity, and its expression has been associated with either pro- or anti-tumour effects in multiple tumour types. In this study, we provide the first evidence that DPP4 expression and enzyme activity are uncoupled under hypoxic conditions in ovarian cancer cells. Whilst we identified strong up-regulation of DPP4 mRNA expression under hypoxic growth, the specific activity of secreted DPP4 was paradoxically decreased. Further investigation revealed matrix metalloproteinases (MMP)-dependent inactivation and proteolytic shedding of DPP4 from the cell surface, mediated by at least MMP10 and MMP13. This is the first report of uncoupled DPP4 expression and activity in ovarian cancer cells, and suggests a previously unrecognized, cell- and tissue-type-dependent mechanism for the regulation of DPP4 in solid tumours. Further studies are necessary to identify the functional consequences of DPP4 processing and its potential prognostic or therapeutic value.
