A recent study from the University of Helsinki sheds new light on the behavior of the KRAS gene in two of the most deadly cancers: pancreatic and colorectal cancer. These findings suggest a potential pathway for targeted therapy in KRAS-driven cancers.
KRAS is a gene known to be mutated in a variety of cancers, with effects that are more complex than previously understood. Although the role of mutant KRAS in causing cancer is well known, this new study highlights the importance of the presence or absence of normal, non-mutant KRAS.
A team led by Dr. Arafath (Rafa) Najumudeen used both mouse models and patient data to study the impact of KRAS on tumor development, progression, and treatment response in pancreatic and colorectal cancer.
The study, published in Cancer Research and Nature Communications, demonstrates that deletion of the normal version of the KRAS gene can accelerate the growth of pancreatic and colorectal cancers. Interestingly, these tumors appear to be less likely to metastasize.
We discovered that the normal version of KRAS acts like a cancer brake, suppressing the effects of mutated KRAS genes that promote cancer growth. ”
Lead author of the study, Dr. Rafa Najmudeen from the Finnish Institute of Molecular Medicine (FIMM), University of Helsinki
The results also suggest that when a patient’s pancreatic cancer loses the normal KRAS gene, the cancer becomes more sensitive to a class of drugs called MEK inhibitors. This means that patients with a specific genetic profile, those who have lost their normal KRAS gene, may be more likely to benefit from targeted therapies that slow tumor growth.
“Our findings provide a deeper understanding of how different versions of the KRAS gene interact in cancer. More importantly, these studies support the development of two highly malignant “This provides a path to potentially more effective treatments for advanced cancers,” added Dr. Najmudeen. “These cancers are often diagnosed late and difficult to treat, so new discoveries are critical to improving patient outcomes. By targeting tumors with specific genetic profiles, It can give patients a better chance of survival.”
Pancreatic and colorectal cancers are the leading causes of cancer-related deaths worldwide. This research opens new opportunities for targeted therapy and could lead to more effective treatments for many cancer patients in Finland and around the world.
“KRAS has long been the focus of international research, with most research focusing on the biology of the mutated KRAS gene and its inhibition with drugs. This new study shows that in cancer, normal KRAS This is groundbreaking because it shows that the gene is normal, and plays an important role in cancer control and the effectiveness of drug therapy, rather than just a bystander.” Johanna Obaska, professor of molecular and cell biology at the University of Turku, commented:
The study was carried out in collaboration with the Scottish Institute for Cancer Research UK and supported by the Finnish Research Council, the Sigrid Juselius Foundation and the Cancer Foundation.
sauce:
Helsingin Iliopist (University of Helsinki)
Reference magazines:
Fay, S. K., et al. (2024). Loss of KRAS heterozygosity promotes MAPK-dependent pancreatic ductal adenocarcinoma development and induces therapeutic sensitivity to MEK inhibition. Cancer research. doi.org/10.1158/0008-5472.can-23-2709.
