- Researchers at The Institute of Cancer Research (ICR), London are reporting that cancer cells have the ability to change their size to adapt to various challenges in their environment, including drug treatment.
- By using biochemical profiling and mathematical analysis, the researchers identified genetic changes that contribute to the size differences in cancer cells.
- The research suggests that smaller cancer cells could be targeted with chemotherapy and targeted drugs, while larger cancer cells may respond better to immunotherapy.
A new study, published in the journal Science Advances and funded by The Institute of Cancer Research, is using advanced image analysis and DNA/protein examination to investigate the size regulation of melanoma cells, a type of skin cancer.
Melanoma can be caused by distinct genetic mutations. Two of the most common are a BRAF gene mutation, which is present in about 50% of cases, and an NRAS mutation, which is found in about 25% of cases.
Cancer cells with different mutations can have different sizes. Smaller cells have more proteins that can fix their DNA when it gets damaged, so they can handle more damage than larger cells.
The researchers reported that drugs that block DNA repair proteins, combined with chemotherapy, might work well against the smaller cancer cells.
However, larger cancer cells accumulate DNA damage and mutations, making them less dependent on DNA repair machinery. This means that the same drugs might not work as well against them.
The size of cancer cells can differ depending on the mutation, with BRAF-mutant cells being small and NRAS-mutant cells being large, especially those resistant to drugs.
Smaller cells have more DNA repair proteins, which makes them better equipped to handle DNA damage. The researchers suggest that using drugs that block these repair proteins, such as PARP inhibitors, combined with chemotherapy, may be more effective against smaller cells.
Larger NRAS-mutant cancer cells accumulate mutations and DNA damage, so they may not depend as much on DNA repair machinery, making chemotherapy and PARP inhibitors less effective against them.
Targeting larger cancer cells may boost immunotherapy
The researchers suggest that larger cancer cells may be better targets for immunotherapy because they have more mutations, which could make them appear more foreign to the body.
Further studies are being conducted to explore this theory.
The study concentrated on skin cancer cells, but the researchers say that the ability of cancer cells to change size and how that affects treatment response is common across multiple cancer types.
They say they have already found similar mechanisms in breast cancer and are currently investigating whether this discovery could be applied to head and neck cancers. This finding helps explain how cell size affects cancer and predict how people with cancer will respond to different treatments just by analyzing cell size.
This could also help improve the effectiveness of treatments such as immunotherapy or radiotherapy by using existing drugs to manipulate cancer cells into a desired size.
Cancer cells change in size
Professor Chris Bakal, the lead author of the study and a cancer morphodynamics professor at The Institute of Cancer Research, explained the key findings to Medical News Today, saying “we found that cancer cells can shrink or super-size themselves to survive drug treatment or other challenges within their environment.”
We used image analysis and proteomics to show for the first time that certain genetic and protein changes lead to a controlled change in the size of cancer cells. For example, protein changes which allow cancer cells to shrink or grow may also enable cancer cells to better repair or withstand DNA damage caused by treatments like chemotherapy – meaning they become resistant to the treatment. This means we may be able to predict how cancer cells will respond to treatment based on their size.
Professor Chris Bakal
What are the implications for future treatments?
Bakal explained that this research has implications for how people are treated, telling MNT that “in the future, pathologists may be able to look at cell size to predict whether a drug will work, or if the cells will resist treatment. In the future, it may even be possible to use [artificial intelligence] to help guide pathologists so they can make rapid treatment decisions based on cell size.”
Our work suggests that smaller cells could be more vulnerable to DNA-damaging agents like chemotherapy combined with targeted drugs, while larger cancer cells might respond better to immunotherapy.
Professor Chris Bakal
Dr. Dung Trinh, the chief medical officer at Healthy Brain Clinic who was not involved in this research, told MNT that “this research on cancer cell size and proliferation control adds to our knowledge base that cancer mutations are not completely random but rather a definitive act for survival.”
The study found that cancer cells with smaller proteomes are able to overcome the limitations of nutrient availability and support their survival by repurposing metabolic pathways. This further supports the idea that cancer cells are not simply a product of random mutations, but rather the result of a complex and dynamic process of cellular adaptation and selection.
Dr. Dung Trinh
Bakal noted there were limitations to the study. For example, “the data we analyzed was from common melanomas, but for rarer types of melanomas – or certainly other cancers – we need to prove the same principles apply,” he said.
However, Bakal did highlight that they had “good clues from patients with xeroderma pigmentosum and breast cancer that the same principles hold.”
Xeroderma pigmentosum, also called XP, is a genetic condition that involves a decreased ability of the skin to repair DNA damage, including from the sun, and it can lead to skin cancer.
Trinh agreed, saying that “the implications of this research are significant for both patients and the public.”
“For patients, this research may lead to the development of more effective and targeted therapies that specifically address the mechanisms controlling cancer cell size and proliferation. This could potentially improve treatment outcomes, reduce side effects, and increase survival rates for people with cancer,” he said.
“For the public, [it may] provide a better understanding of the underlying mechanisms of cancer, which could lead to earlier detection and prevention of the disease. It could also lead to the development of new diagnostic tools and biomarkers that help identify high-risk individuals and inform treatment decisions,” Trinh added.
In conclusion, Trinh said, “this research provides valuable insights into the complex biology of cancer and has the potential to improve cancer treatment and patient outcomes, as well as advance our understanding of the disease for the benefit of public health.”
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