Summary of Tumor Cells’ Response to Treatment Is Driven by Randomness:
New research from the Garvan Institute of Medical Research has shown that cancer cells have an inbuilt randomness in their ability to respond to chemotherapy, a tool that they use to resist treatment. The researchers found that there is inherent noise in the process of cell death that happens to cancer cells during chemotherapy treatment, and that this randomness in the system of gene expression is an important aspect of chemoresistance. The findings suggest that genetics don’t account for everything and other mechanisms of tumor progression can underpin drug response. The team identified certain classes of approved drugs that might be combined with chemotherapy to stabilize expression of the genes involved in cell death, or by changing the innate threshold that may tip a tumor cell into a resistant state.
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The fight against cancer continues to be a challenging battle. Despite extensive research and the development of new treatments, cancer remains a leading cause of death worldwide. One of the biggest challenges in cancer research is understanding why some tumors become resistant to chemotherapy. A recent study led by the Garvan Institute of Medical Research in Australia sheds new light on this issue and highlights the importance of considering the inherent ‘noise’ in the system of gene expression in tumor cell death.
The study focused on neuroblastoma, a type of cancer that develops in the body’s ‘fight or flight’ sympathetic nervous system. According to the researchers, about 15% of people with neuroblastoma do not respond to chemotherapy treatment. The team used mathematical modeling to identify the ‘noise’ signals in the pathways of cell death in neuroblastoma tumors. They then looked at patient cell samples, using cutting-edge imaging to isolate the cells that did not respond to treatment.
The researchers found that there is an inherent randomness in the process of cell death, which is what happens to cancer cells with chemotherapy treatment. This randomness, or noise, in the system of gene expression makes it difficult to predict how tumor cells will respond to chemotherapy. In effect, cancer cells use this noise to resist chemotherapy treatment.
“We showed that this randomness in the system of gene expression is an important aspect of chemoresistance,” says Associate Professor David Croucher, Head of the Network Biology Lab at Garvan. “Our findings suggest that there is a small window where treatment could work on a tumor cell before it’s locked into a state of resistance.”
The team found a marker for resistance – a set of proteins involved in the process of cell death, known as apoptosis. The researchers suggest that combining chemotherapy with drugs that target this noise within tumors may have the best results as a first-line treatment after diagnosis, before tumors lock into a state of resistance. This approach would flip the typical protocol for clinical trials in cancer where a new treatment is given to patients who have exhausted all other treatment options.
The study highlights the importance of considering other layers of regulation and other mechanisms of tumor progression that can also underpin drug response. Genes alone do not account for everything. There are other factors, such as randomness and noise, that play a significant role in cancer cells’ ability to resist treatment.
The researchers hope to progress their work to clinical trials soon. The ultimate goal is to develop new and more effective treatments that can target the randomness and noise in tumor cells, giving cancer patients a better chance of survival.
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