Cancer cells can change size to escape treatment, say scientists

Cancer cells can change size to escape treatment, scientists have discovered.

The new findings could lead to better use of the treatment, while a new therapy could slow the disease by focusing on proteins involved in regulating cell size.

Experts at the Cancer Research Institute in London combined biochemical profiling technology with mathematical work to show how genetic changes lead to differences in the size of cancer cells.

Researchers believe that smaller cells may be more vulnerable to agents that damage DNA, such as chemotherapy combined with drugs, while larger cells may respond better to immunotherapy, which harnesses the power of a patient’s immune system.

The study, published in the journal Advances in Scienceinvolved examining millions of skin cancer cells.

But the team believes their findings could also apply to other types of cancer. They have already identified similar mechanisms in breast cancer and are now looking at head and neck cancers.

“This intriguing and pivotal study provides a correlation between genetic changes in skin cancer cells and cell size,” said Professor Kristian Helin, Executive Director of the ICR.

“It opens up the potential of using genetic changes and cell size as biomarkers of how skin cancer will respond to treatments.

“It is particularly exciting that cell size could also be an important biomarker of how other cancers, such as breast or head and neck, respond to treatments.”

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The researchers investigated differences in the size and shape of skin cancer cells that harbor two genetic mutations.

Skin cancer melanoma is caused by two different gene mutations, with 60% of cases caused by one known as BRAF and 20 to 30% caused by one called NRAS.

The study found a big difference in the size of the cells. The BRAF mutant cancer cells were very small, while the NRAS mutant cancer cells were much larger and the drug-resistant NRAS cells even larger.

Experts said that smaller cells appear to be able to tolerate higher levels of DNA damage due to a high concentration of proteins that repair DNA.

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This means that these cells can be attacked with chemotherapy and drugs like PARP inhibitors, which block proteins responsible for repairing DNA damage.

In contrast, the larger NRAS mutant cancer cells contained DNA damage rather than repairing it, meaning that chemotherapy and PARP inhibitors may not be as effective.

Scientists believe that these larger cells may be more responsive to immunotherapy.

“We think of cancer as something out of control and unpredictable, but we used imaging analysis and proteomics (the study of proteins) to show for the first time that certain genetic and protein changes lead to a controlled change in the size of cancer cells,” he said. the leader of the study, Prof. Chris Bakal.

“Cancer cells can shrink or grow to increase their ability to repair or contain DNA damage, which in turn can make them resistant to certain treatments.

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“We think our research has real diagnostic potential. By looking at cell size, pathologists can predict whether a drug will work or whether cells will be resistant.

“In the future, it may even be possible to use AI to help guide the pathologist, making a quick assessment of cell size and thus the treatments most likely to work.

“We also hope that our discovery will lead to new treatment strategies – for example, the creation of drugs to target proteins that regulate cell size.”

Updated: January 25, 2023, 9:49 PM

Cancer cells can change size to escape treatment, say scientists

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