The cancer cells are relentless, have 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 spot, his 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 its destruction. The work of chromatin (the way in which DNA is presented in the nucleus of cells) is to carefully pack the genetic code into the nucleus of the cell. It can also regulate which genes are ‘turned on and off’. In cancer cells, however, chromatin helps these cells evolve, allowing them to survive.
“If you think of genetics as hardware, chromatin is software, “explains Vadim Backman, co-author of the paper.”Complex diseases such as cancer do not depend on the behavior of individual genes, but on the complex interaction between tens of thousands of genes.”
That’s why experts decided to focus on chromatin as a key tool to combat 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 scale of 20-200 nanometers in length, the precise point at which the formation of cancer influences in chromatin.
Using this novel technique to monitor chromatin in cultured cancer cells, they discovered that chromatin has a specific “packaging density” related to gene expression that helps cancer cells to evade treatments.
The analysis revealed that a more heterogeneous and disorganized packing density of the chromatin caused a greater survival of the cancer cells in response to the chemotherapy. However, a more conservative and orderly packing density was associated with a greater death of cancer cells in response to chemotherapy.
“Just looking at the structure of the cell’s chromatin, we could predict if it would survive or not,” says Backman.
Based on this discovery, researchers hypothesized that an lterar the chromatin structure to make it neater could be a way to increase susceptibility of cancer cells to treatment. They got 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:
“In 2 or 3 days, almost all the cancer cells died because they could not respond.” CPT compounds – Celecoxib and Digoxin – do not kill cells, but restructure chromatin – if you block the ability of cells to evolve and adapt, that it’s your Achilles heel, “explains Backman.
While researchers are enthusiastic about their findings, they caution that studies in animals and humans are needed before firm conclusions can be drawn.
“There is a big difference between cell cultures and humans, we never know how the environment inside the human body will affect the behavior of the cancer or if there will be unforeseen side effects,” explains Backman.
Be that as it may, it looks really promising.