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In a whole new approach to cancer treatment, Northwestern University biomedical engineers claim to have doubled the impact of chemotherapy in pre-clinical trials. Instead of trying to attack cancer directly, as is the case with conventional chemotherapy, the new strategy instead blocks the cancer cells from evolving and hence making sure that they don't become untreatable.
Doubling The Impact of Chemotherapy
The study published in the journal Proceedings of the National Academy of Sciences was led by Vadim Backman, who is a Professor of Biomedical Engineering and Medicine at Northwestern’s McCormick School of Engineering. The study claimed that as the new strategy blocks the cancer cells from evolving, it therefore renders it treatable with already available drugs, because it takes away the resistance from the cancerous cells. It is pertinent to mention that once the cells evolve, they tend to become resistant to cancer drugs and the effect of chemotherapy becomes limited. As per the scientists, the new method not only nearly completely eradicated the disease in cellular cultures, but it also significantly improved chemotherapy's efficacy in mouse models of human ovarian cancer.
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The study's lead researcher, Vadim Backman stated that cancer cells are excellent adapters. and that they are able to adjust to nearly anything that is thrown at them. “They start by learning how to avoid the immune system. They then learn how to adjust to radiation, immunotherapy, and chemotherapy. They develop mutations and live longer when they reject these treatments. Killing cancer cells directly was not our goal. Our goal was to eliminate their superpower, which is their innate capacity for adaptation, change, and escape,” he added.
The Key To Cancer Survival?
The group of macromolecules known as chromatin, which includes proteins, RNA, and DNA, controls which genes are expressed or suppressed. Chromatin is packed very tightly inside the nucleus of a cell to fit the two meters of DNA that make up the genome into a hundredth of a millimetre of space. Backman's team used imaging, simulations, systems modelling, and in vivo experiments to find that the three-dimensional architecture of this packing not only regulates which genes are expressed and how cells react to stress, but also enables cells to physically encode memories of gene transcription patterns into the packing's geometry.
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“Similar to a machine learning algorithm, the genome's three-dimensional arrangement functions as a self-learning system. This configuration continuously changes into thousands of nanoscopic chromatin packing domains as it gains knowledge. Part of a cell's transcriptional memory, which controls how the cell operates, is stored in each domain. These cell-specific chromatin domains are created, reinforced by cellular experiences, stored, and rewritten over the course of a person's lifetime. Issues with this transcriptional memory may contribute to ageing and cause conditions like cancer and Alzheimer's disease.
When chromatin packing is disrupted in cancer, a cell exhibits greater plasticity, or adaptability, which helps the cell learn to withstand chemotherapy and other treatments,” the study said.
Manipulating Chromatin
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Celecoxib and related medications may develop into a novel class of substances known as Transcriptional Plasticity Regulators (TPRs), which alter chromatin conformation to stop cancer cells from adapting, claims Backman. The number of cancer cells that perished significantly increased when celecoxib was added to conventional chemotherapy, the researchers discovered. Backman and his group wanted to show its potential in a more realistic biological system after demonstrating its efficacy in cellular cultures. Using a mouse model of ovarian cancer, the team combined celecoxib with paclitaxel, a common chemotherapy drug. The combination outperformed paclitaxel alone in the experiments, lowering the adaptation rates of the cancer cells and improving the inhibition of tumour growth twice than the conventional treatments.
Bottomline
Although the research has only so far concentrated on cancer, the scientists believe that altering chromatin conformation may hold the key to treating a number of complex illnesses, such as heart disease, neurodegenerative diseases, and more. A multicellular organism has hundreds of different cell types, including bone, neurones, skin, heart tissue, blood, and so forth, even though the majority of its cells have the same genome.