Researchers have found that cancer cells may supersize themselves or shrink as they try to survive drug treatment or environmental challenges.
The Institute of Cancer Research scientists in London combined biochemical tech with mathematical analyses to show how genetic changes can result in differences in cancer cell size. These changes can be leveraged in the development of new treatments.
Small cancer cells vulnerable to DNA-damaging agents like chemotherapy
Researchers say smaller cells may be susceptible to DNA-damaging agents such as chemotherapy and targeted medicines, whereas large cancer cells could respond well to immunotherapy. The study published in the Science Advances journal combines high-powered, innovative image analysis with DNA and protein examination to study size control in skin cancer cells.
Two genetic mutations lead to skin cancer melanoma, with 60% of the cases attributed to BRAF gene mutation and 20%-30% attributed to NRAS mutation. The researchers investigated the differences in shape and size of skin cancer cells that harbor the two gene mutations. They employed mathematical algorithms in analyzing considerable amounts of DNA and protein data.
The difference between BRAF and NRAS mutant cells is cell size
Cell size was the main difference, with BRAF-mutant cells being very small while NRAS-mutant cancer was bigger. Interestingly, drug-resistant NRAS cancer cells were much bigger. The small ones seem resistant to DNA damage since they are concentrated with DNA repair proteins like ATM1, PARP, and BRCA proteins.
According to ICR researchers, this may make them vulnerable to treatments such as PARP inhibitors, particularly when combining them with DNA-damaging treatments like chemotherapy. PARP inhibitors are drugs that block proteins that repair DNA damage.
On the other hand, the bugger NRAS-mutant cancer cells had DNA damage rather than repairing its enlarging and accumulation mutations. Surprisingly, the larger cells didn’t rely on DNA repair mechanisms, and this use of PARP inhibitors and chemo may not be effective.
According to researchers, NRAS and BRAF mutations could be responsible for the differences in cell size through protein-level regulation.
