Researchers and oncologists are continually challenged by breast cancer that recurs or spreads, despite advances in cancer detection and therapy.
The American Cancer Society projects that 44,130 Americans will pass away in 2021 from recurrent or metastatic breast cancer. Patients’ ten-year survival rates plummet from 93% to 27% if the cancer returns, and to 7% if it returns and spreads to other regions of the body.
University of Cincinnati and Cincinnati Children’s Hospital Medical Center researchers are investigating the biology of breast cancer recurrence. The team led by Susan Waltz, PhD, of the University of California and Susanne Wells, PhD, of Cincinnati Children’s Hospital Medical Center presented recent results on biomarkers that help predict outcomes and could be targets for novel treatments in the Sept. 6 issue of PLOS ONE.
Both research groups were studying distinct oncogenes, or genes that promote the growth of cancer cells, dubbed Ron and DEK, when the relationship began approximately 15 years ago, according to Waltz.
We demonstrated that both Ron and DEK play a significant role in breast cancer and are independently related with poor overall survival in breast cancer patients. We know that the genes Ron and DEK are crucial for predicting breast cancer recurrence, but there are currently no effective treatments that target DEK.”
Current study centred on the importance of metabolic plasticity, or how the body’s metabolism is always changing, which plays a crucial part in how cancer grows and recurs.
The research team discovered that the Ron and DEK genes can regulate specific metabolites, compounds produced or utilised when the body breaks down food, medications, or chemicals, in order to promote the growth and spread of cancer cells.
By analysing the implicated enzymes, the scientists established a metabolic signature that can be used to more accurately predict patient outcomes. In addition to being a useful biomarker, the metabolic signature itself could be an attractive therapeutic target.
For instance, if a high level of a certain enzyme is predictive of favourable outcomes, nutritional supplements or other treatments can be used to stimulate the activity of that enzyme. Alternately, if high levels of a particular metabolite are predictive of poorer results, therapies can lower that metabolite by inhibiting the relevant enzymes in that pathway.
Waltz stated that future research will examine how Ron and DEK influence other molecules, such as lipids or fatty acids, that play a role in metabolism. By characterising even more specific metabolic signatures that correlate with breast cancer patient outcomes, other therapy paths may be discovered.
Waltz and Wells reported that the relationship between their labs has expanded beyond research to include more collaborative talks and training of students and lab personnel.
The researchers were also assisted by the NMR-based Metabolomics Core at Cincinnati Children’s, a facility that enables researchers doing metabolism-related research with cutting-edge technologies.
Waltz and Wells highlighted the contribution of Sara Vicente-Muoz, co-first author on the study and research associate at Cincinnati Children’s in the Metabolomics Core, to the advancement of research.
Journal reference: Vicente-Muñoz, S., et al (2022) A NMR-based metabolomic analysis identifies metabolic pathways dependent on RON-DEK—catenin and a gene signature that stratifies breast cancer patient survival. PLOS ONE. doi.org/10.1371/journal.pone.0274128.
Vicente-Muñoz, S., et al. (2022) NMR-based metabolomic analysis identifies RON-DEK-β-catenin dependent metabolic pathways and a gene signature that stratifies breast cancer patient survival. PLOS ONE. doi.org/10.1371/journal.pone.0274128.