The size of skin cancer cells may affect how they respond to treatment
Smaller melanoma skin cancer cells may be more vulnerable to drugs that block DNA repair, while larger cells might be more responsive to immunotherapy
26 January 2023
Certain skin cancer cells may differ in how they respond to various treatments according to their size. Better understanding this and how it relates to treatment outcomes could help doctors predict an individual’s drug response.
Cancer cells were generally assumed to be “a hodgepodge of different sizes”, says Chris Bakal at The Institute of Cancer Research in London.
To investigate this, Bakal and his colleagues used high-powered imaging to gauge how genetic changes affect the size of millions of melanoma cells caused by two mutations, affecting the BRAF or NRAS genes. Melanoma develops from skin cells called melanocytes and is the most serious type of skin cancer.
They found that the smallest cells were around 17 micrometres (μm) across, while the largest were 50μm across, on average.
The smaller cells contained higher levels of proteins that repair DNA, suggesting that they can tolerate more DNA damage. These cells may therefore be more vulnerable to drugs that block DNA repair, particularly if combined with chemotherapy, which damages DNA, says Bakal.
The bigger cells contained damage to their DNA and were less reliant on DNA repair techniques. This may make chemotherapy less effective, according to the researchers.
Instead, larger cells would probably respond more to immunotherapy if they appear “more alien” to the immune system, according to the team. Immunotherapy helps the immune system to recognise and attack cancer cells.
Based on previous research into the role of proteins in cancer cells, the researchers suspect that these mutations primarily affect a protein called CCND1. This is involved in interactions with other proteins, as well as cell division, growth and the maintenance of their shape, which may explain why some mutations are linked to cell size, says Bakal.
The researchers are investigating whether similar results could apply to head and neck cancers.
Creating a treatment strategy based on the size of melanoma cells could help lessen the side effects experienced by some people while taking cancer drugs, says Bakal. “We rarely want to give patients everything and bombard them.”
The results could also improve our understanding of cancer cells in general.
“I think the idea that they’re very actively controlling their size is pointing us in a different way to think about cancer,” says Bakal. “They still exert some level of control on their shape and their size. They have a ‘plan’.”
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