Researchers at UNC Lineberger Comprehensive Cancer Center and their colleagues have conducted a comprehensive study to understand the molecular workings of KRAS, a gene that is known to cause cancer. This gene is commonly mutated in human cancers, and it is present in over 90% of pancreatic cancer tumors. Despite its prevalence, the exact mechanisms through which KRAS promotes cancer growth are not well understood. To address this gap in knowledge, the researchers have worked extensively to identify the other genes and proteins that contribute to the lethal effects of KRAS expression.The researchers have provided a comprehensive molecular portrait of KRAS, a cancer-causing gene, and its impact on pancreatic cancer outcomes. This could potentially lead to improved treatment options for pancreatic cancer, which is the third leading cause of cancer deaths in the United States.
The research findings were published in two separate articles in Science.
“Less than 40% of pancreatic cancers respond to treatment with KRAS inhibitors. If we can identify molecular markers to predict which patients will respond, we can provide them with more targeted treatment.”According to UNC Lineberger’s Channing J. Der, PhD, a Sarah Graham Kenan Distinguished Professor at UNC School of Medicine’s Department of Pharmacology and a corresponding author of both articles, the treatments being developed should improve the outcomes for pancreatic cancer patients. The average patient treated with chemotherapy lives for 6 to 12 months from diagnosis to death, so there is a limited window for effective treatment.
KRAS is a frequently mutated gene in human cancers, and it is present in over 90% of pancreatic cancer tumors. However, the exact mechanism by which it promotes cancer growth is not well understood. This is why researchers at UNC Lineberger are focusing on studying it.Researchers have begun a thorough investigation to identify the other genes and proteins that contribute to the harmful effects of KRAS expression.
In their most comprehensive analysis to date, they found that the molecular pathway responsible for the cancer-driving abilities of KRAS relies heavily on a protein called ERK. This protein has dual functions in controlling gene expression and protein activity. While ERK has been extensively studied in cancer research and its role in KRAS function is well-known, its exact importance and how it carries out its role have remained unclear.The Science papers revealed that the activation of the ERK protein is the main cause of resistance to drugs that target KRAS. With better ways to study cellular signaling, researchers showed that the ERK protein controls the expression of thousands of genes and affects the activity of thousands of proteins. The researchers also found that their discoveries in cancer models could accurately predict responses in patients being treated for pancreatic, colorectal, and lung cancers with ERK and KRAS therapies. As of now, two KRAS drugs have been developed.treatments,” said Der. “We are also working on developing new therapeutic strategies that target MYC and other key players in the KRAS pathway.”
The research team’s findings have significant implications for the development of more effective therapies for KRAS-driven cancers. By understanding the relationship between MYC and KRAS, researchers can potentially develop combination therapies that target both pathways, overcoming the issue of resistance.
the recent findings shed light on the complexities of KRAS-driven cancer and provide new hope for developing more successful treatments in the future.,” Der said that the focus will remain on utilizing the expanding scientific knowledge to further the clinical development of more effective KRAS inhibitors,”