CHICAGO, Nov. 9 (Xinhua) -- Researchers at Northwestern University (NU) have developed an effective new strategy for treating cancer: controlling cells' chromatin to prevent cancer from adapting to treatment, the study has been newly published in Nature Biomedical Engineering.
And the new strategy has wiped out the disease to near completion in cellular cultures in the laboratory.
NU researchers did not rely on discovering new drugs or treatment options. Instead they aim to stop cancer's adaptive behavior to boost the effectiveness of current treatments.
The treatment works by controlling chromatin, a group of macromolecules including DNA, RNA, and proteins that houses genetic information within cells and determines which genes get suppressed or expressed. In the case of cancer, chromatin has the ability to regulate the capacity of cancer cells to find ways to adapt to treatment by expressing genes that allow the cancer cells to become resistant to treatment.
Found in cells, chromatin is a disordered chain polymer that is packed together at different densities throughout a cell's nucleus. Through a combination of imaging, simulations, systems modeling, and in vivo experiments, NU researchers discovered that this packing-density of chromatin in cancer cells produced predictable changes in gene expression: the more heterogeneous and disordered the packing density, the more likely cancer cells were to survive, even in the face of chemotherapy; the more ordered and conservative the packing density, the more likely the cells would die from cancer treatment.
Throughout the study, NU researchers realized that they could control chromatin by changing the electrolytes present in the cell's nucleus. They used two drugs, namely Celecoxib and Digoxin, both FDA-approved immunological agents already on the market and having a side effect of altering chromatin packing density.
They combined these compounds named "chromatin protection therapeutics" or CPT compounds with chemotherapy to treat seven different types of cancer in cell cultures.
"Within two or three days, nearly every single cancer cell died because they could not respond," said Vadim Backman, biomedical engineering professor at NU McCormick School of Engineering. "The CPT compounds don' t kill the cells; they restructure the chromatin. If you block the cells' ability to evolve and to adapt, that's their Achilles' heel."
"If you think of genetics as hardware, then chromatin is the software," said Backman. "Complex diseases such as cancer do not depend on the behavior of individual genes, but on the complex interplay among tens of thousands of genes. By targeting chromatin, we can modulate global patterns in gene expression."
The treatment is now undergoing studies in an animal model.
