The size of skin cancer cells may affect how they respond to treatment

Smaller melanoma skin cancer cells may be more vulnerable to DNA repair blocking drugs, while larger cells may be more sensitive to immunotherapy.

Some skin cancer cells may respond differently to different treatments depending on their size. A better understanding of this, and how it relates to treatment outcomes, can help doctors predict a person’s response to a drug.

It was generally assumed that cancer cells were “hodgepodges of various sizes,” says Chris Bakal of the Institute for Cancer Research in London.

To explore this, Bakal and colleagues used high-performance imaging to evaluate how genetic changes affect the size of millions of melanoma cells caused by two mutations that affect BRAF or NRAC genes. Melanoma develops from skin cells called melanocytes and is the most serious type of skin cancer.

They found that the smallest cells measured about 17 micrometers (µm) across, while the largest averaged 50 µm.

The smaller cells contained higher levels of proteins that repair DNA, suggesting they could tolerate more DNA damage. Therefore, these cells may be more vulnerable to drugs that block DNA repair, especially when combined with chemotherapy that damages DNA, Bakal says.

Larger cells contained damage to their DNA and were less dependent on DNA repair techniques. According to the researchers, this could make chemotherapy less effective.

Instead, the team says, larger cells are likely to respond more to immunotherapy if they appear “more foreign” to the immune system. Immunotherapy helps the immune system recognize and attack cancer cells.

Based on previous studies on the role of proteins in cancer cells, the researchers suspect that these mutations primarily affect a protein called CCND1. It is involved in interactions with other proteins and in cell division, growth, and maintenance of shape, which may explain why some mutations are related to cell size, Bakal says.

The researchers are investigating whether similar findings could apply to head and neck cancer.

Creating a treatment strategy based on the size of melanoma cells could help reduce the side effects some people experience when taking anti-cancer drugs, Bacal said. “We rarely want to give our patients everything and bombard them.”

The results may also improve our understanding of cancer cells in general.

“I think the idea that they are very actively controlling their size makes us look at cancer in a new way,” Bakal says. “They still have some control over their shape and size. They have a “plan”.