The journal Nature Biomedical Engineering published a study which revealed that alterations of the chromatin structure in cancer can make them easier to destroy.
Chromatin is formed by the DNA that is wraps around proteins called histones in the cell nucleus.
The function of chromatins are to package the genetic code neatly into the cell’s nucleus. The genes that are turned on and off are regulated from chromatin. It is also responsible for the adaption and evolution of cancer cells, explaining why cancer cells can survive after cancer therapies.
“If you think of genetics as hardware,” explains study co-author Vadim Backman, of the McCormick School of Engineering at Northwestern University in Evanston, IL, “then chromatin is the software.”
“Complex diseases such as cancer,” he adds, “do not depend on the behavior of individual genes, but on the complex interplay among tens of thousands of genes.”
Chromatin is the key to ending drug resistance in cancer according to Backman and his colleagues. To better understand this, they developed an imaging technique to help them better understand more about the intricate set of macromolecules.
Predicting cancer cell death with chromatin
PWS (Partial Wave Spectroscopic) microscopy is the name of this new technique which the enables chromatin in living cells to be monitored at real-time.
With PWS, researchers can assess chromatin at a length scale of 20-200 nanometers, the precise point where chromatin is influenced by cancer formation.
Chromatin in cultured cancer cells were monitored through PWS. Specific packing density was associated with gene expression that aided cancer cells to evade treatments was found in chromatin through PWS.
A more heterogeneous and disordered chromatin packing density was linked to cancer cells surviving chemotherapy according to the analysis, while a more conservative and organized packing density showed more deaths of cancer cells from chemotherapy.
“Just by looking at the cell’s chromatin structure, we could predict whether or not it would survive,” says Backman. “Cells with normal chromatin structures die because they can’t respond; they can’t explore their genome in search of resistance. They can’t develop resistance.”
Targeting chromatin to kill cancer
Researchers hypothesized that by changing the chromatin structure to be more organized and conservative could make cancer cells more vulnerable to treatment based on what they discovered.
Through further inspection of this matter, the researchers found that a chromatin’s structure could be altered by modifying the electrolytes in the nucleus of cancer cells.
Celecoxib and Digoxin, two drugs that are already approved by the Food and Drug Administration (FDA) was tested by the research team to prove if this strategy worked .
Celecoxib is medically prescribed by doctors for pain relief, while Digoxin is used by doctors treat atrial fibrillation and heart failure. The packing density of chromatin can be changed by both drugs.
CPTs (chromatin protection therapeutics) is the combination of the two drugs. The researchers then used the CPTs along with chemotherapy and tested them in the laboratory.
The researchers saw “something remarkable” according to Backman.
“Within 2 or 3 days, nearly every single cancer cell died because they could not respond. 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.” said Vadim Backman.
Testings with animal and human test subjects would be needed to conclude this, even though the researchers were thrilled with their results.
“There is a big difference between cell cultures and humans,” says Backman. “You never know how the environment inside the human body will affect cancer’s behavior or if there will be unforeseen side effects.”
The findings from the researchers were replicated in seven different cancer types as of now, all of which Backman finds to be“very promising.”
5th May 18:40