Cancer cells are relentless , possess the ability to develop resistance to current therapies, and make the disease very difficult to treat. However, a new study may have identified the cancer’s weak point, its Achilles heel . So much so that the discovery has already led to the eradication of the disease in cell cultures.
The study, published in the journal Nature Biomedical Engineering , reveals how altering the structure of chromatin in cancer cells could facilitate their destruction. The job of chromatin (the way DNA is presented in the nucleus of cells) is to carefully package the genetic code in the nucleus of the cell. It can also regulate which genes are ‘on and off’. In cancer cells, however, chromatin helps them evolve, allowing them to survive.
“ If you think of genetics as hardware, chromatin is software, ” explains Vadim Backman, co-author of the work. “Complex diseases like cancer do not depend on the behavior of individual genes, but on the complex interaction between tens of thousands of genes.”
That’s why the experts decided to focus on chromatin as a key tool in combating resistance to cancer drugs, and an imaging technique they developed last year helped them learn more about this intricate set of macromolecules.
New technique against cancer
The new technique is called partial wave microscopy and allows real-time monitoring of chromatin in living cells, being able to evaluate chromatin on a length scale of 20-200 nanometers, the precise point at which cancer formation influences in chromatin.
Using this novel technique to monitor chromatin in cultured cancer cells, they discovered that chromatin has a specific “packing density” related to gene expression that helps cancer cells evade treatments.
The analysis revealed that a more heterogeneous and disordered packing density of chromatin led to increased survival of cancer cells in response to chemotherapy. However, a more conservative and orderly packing density was associated with increased cancer cell death in response to chemotherapy.
“Just by looking at the structure of the cell’s chromatin, we could predict whether it would survive or not,” says Backman.
Based on this discovery, researchers hypothesized that lterar the chromatin structure to make it neater could be a way to increase susceptibility of cancer cells to treatment. They achieved this by modifying electrolytes in the nucleus of cancer cells and tested this strategy using two drugs already approved by the Food and Drug Administration (FDA): Celecoxib and Digoxin.
Combining both drugs with chemotherapy, they tested them on cancer cells in the laboratory. The result was more than surprising:
“ Within 2 or 3 days, almost all cancer cells died because they were unable to respond. The CPT compounds – Celecoxib and Digoxin – do not kill cells, but instead restructure chromatin. If you block the cells’ ability to evolve and adapt, that it’s his Achilles heel, “Backman clarifies.
While the researchers are excited about their findings, they caution that animal and human studies are needed before firm conclusions can be reached.
“There is a big difference between cell cultures and humans. You never know how the environment within the human body will affect the behavior of cancer or if there will be any unforeseen side effects,” Backman explains.
Either way, it’s really promising.
Referencia: Macrogenomic engineering via modulation of the scaling of chromatin packing density. Luay M. Almassalha, Greta M. Bauer et al. Nature Biomedical Engineering (2017) DOI: doi:10.1038/s41551-017-0153-2
