Cancer cells can change size to evade treatment, say scientists

Cancer cells can change size to evade treatment, say scientists
Cancer cells can change their size to evade treatment, scientists have discovered. The new findings could lead to treatment being put to better use while new therapy could slow down the disease by focusing on proteins involved in regulating cell size.

Experts at the Institute of Cancer Research London combined biochemical profiling technology with mathematical work to show how genetic changes lead to differences in the size of cancer cells. The researchers believe smaller cells could be more vulnerable to DNA-damaging agents such as chemotherapy combined with drugs, while larger cells might respond better to immunotherapy, which harnesses the power of a patient's immune system.

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

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

“This intriguing, fundamental study provides a correlation between genetic alterations in skin cancer cells and cell size," said Prof Kristian Helin, chief executive of the ICR.

“It opens the potential of using genetic alterations and cell size as biomarkers for how skin cancer will respond to treatments. “It’s particularly exciting that cell size could also be an important biomarker for how other cancers, such as breast or head and neck cancers, respond to treatments.”

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

The skin cancer melanoma is driven by two different genetic mutations, with 60 per cent of cases caused by one known as BRAF, and 20 to 30 per cent caused by one called NRAS.

The study found a major difference in cell size. BRAF-mutant cancer cells were very small, whereas NRAS-mutant cancer cells were much bigger, and drug-resistant NRAS cells bigger still.

The experts said that smaller cells appeared to be able to tolerate higher levels of DNA damage because of a high concentration of proteins that repair DNA.

This means these cells could be attacked with chemotherapy and drugs such as PARP inhibitors, which block the proteins responsible for repairing DNA damage.

In contrast, the larger NRAS-mutant cancer cells contained damage to their DNA instead of repairing it, which means chemotherapy and PARP inhibitors may not be as effective.

Scientists believe these larger cells could be more responsive to immunotherapy.

“We think of cancer as out of control and unpredictable, but we used image analysis and proteomics (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," said the study leader, Prof Chris Bakal.

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

“We think our research has real diagnostic potential. By looking at cell size, pathologists could predict whether a drug will work, or if the cells will be resistant. “In the future, it might even be possible to use AI to help guide the pathologist, by making a rapid assessment about the size of cells and so the treatments that are most likely to work.

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

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