By targeting certain genes that regulate acid levels and iron content in cancer cells, the research team found a new, more efficient way to kill cancer cells deprived of oxygen in solid cancer tumours—representing most human cancers.
“Our hope is that this work will lead to the development of novel targeted therapeutics,” said Dr. Franco Vizeacoumar (PhD), USask oncology professor, researcher with the Saskatchewan Cancer Agency, and co-author of the research paper published in the journal Science Advances.
Solid tumours survive using a supply of oxygen-rich blood from the circulatory system. As the tumours grow and get too large to rely on blood vessels for sustenance, they “re-wire” themselves to thrive in a low-oxygen environment, accumulating acid, growing rapidly, and spreading to other organs.
Using CRISPR genome editing technology, the research team checked each of 20,000 genes within the human genome to identify the specific pair of genes responsible for an enzyme critical to protecting and keeping the tumours alive.
By inhibiting that enzyme, iron accumulates in the cancer cells, disrupting the cells’ metabolism, rupturing their membranes, and killing them.
“Our lab worked with Dr. Shoukat Dedhar’s (PhD) lab at University of British Columbia to identify potential combinations of genes that may cause genetic vulnerability in triple negative breast cancer cells,” said Vizeacoumar.
Triple negative breast cancer is an aggressive form of the disease that does not respond to common therapies targeting estrogen, progesterone, or the HER2 protein.
“Our work has identified new roles for certain molecular components in tumour hypoxia—the cross-talk between these and other known components are yet to be determined,” said Vizeacoumar. “Understanding this will enable the design of effective therapies that can also overcome drug resistance.”
The research team includes USask scientist Frederick Vizeacoumar, director of USask’s Phenogenomic Imaging Centre Core facility and brother of Franco, and researchers from University of British Columbia, BC Cancer Research Institute, Pancreas Centre BC, Harvard Medical School in Boston, Mass., and University of Florence, Italy.
The research was supported by funding from the Canadian Institutes of Health Research, Canada Foundation for Innovation, USask College of Medicine, and the Saskatchewan Cancer Agency.
Link to the paper: https://advances.sciencemag.org/lookup/doi/10.1126/sciadv.abj0364