MADRID – After decades of limited progress, researchers are reporting notable advancements in the fight against pancreatic cancer, a disease with a dismal five-year survival rate of less than 5% [[3]]. Experts at the National Cancer Research Center (CNIO) in Madrid are focusing on new therapies targeting the KRAS oncogene and innovative diagnostic tools, offering a glimmer of hope for patients facing this historically challenging diagnosis, notably as incidence rates appear to be rising. These developments, coinciding with World Pancreatic Cancer day, mark a turning point in research efforts that were once hampered by the complexity of the disease [[2]].
MADRID, November 20 –
Recent advances in pancreatic cancer research over the past two decades have significantly improved our molecular understanding of this challenging disease. Experts at the National Cancer Research Center (CNIO) in Madrid say this progress offers new hope for patients facing a historically difficult diagnosis.
Researchers Mariano Barbacid and Carmen Guerra highlighted the “impressive” strides made in the field, noting that while personalized therapies and immunotherapies aren’t yet widely available, the landscape is beginning to shift after decades with limited treatment options. Pancreatic cancer remains a significant public health concern due to its aggressive nature and often late-stage diagnosis.
Among the most promising developments are the first drugs targeting the KRAS oncogene, which is mutated in approximately 90% of patients with the most common form of pancreatic cancer. These drugs are currently in clinical trials and have shown “modest” efficacy, but researchers believe they represent a “valuable pathway” toward more effective and less toxic treatments.
“KRAS inhibitors are performing better than chemotherapy, but ultimately, resistance develops,” explained Guerra on Thursday, coinciding with World Pancreatic Cancer Day. “That’s why we’re investigating the molecular mechanisms of these resistances, to learn how to overcome them.”
Francisco X. Real, a CNIO researcher and president of the Spanish Alliance for Pancreatic Cancer Research (ALIPANC), noted that the lack of clinical progress for decades discouraged young scientists from entering the field, viewing it as “an insurmountable challenge” and “too difficult.” However, that perception is changing.
Improved animal models and other advancements have attracted “a generation of young, exceptionally talented researchers in Spain, eager to combine basic and translational research for the benefit of patients,” Real said.
Despite these advancements, pancreatic cancer remains a major challenge for oncologists, particularly as its incidence appears to be increasing, potentially even among younger individuals. Survival rates remain stubbornly low.
Less than 5% of patients survive five years after diagnosis, largely because the cancer is typically detected at advanced stages when it is no longer operable. Current treatment options largely rely on decades-old drugs with limited effectiveness.
TOWARD EARLY DIAGNOSIS
Researchers are now focusing on prevention and early diagnosis, an area once considered “an impossible dream.” Unlike lung cancer, which is strongly linked to smoking, or cancers with clear genetic predispositions, pancreatic cancer appears to be the result of a complex interplay of numerous factors, many of which remain unknown.
However, enough information is now available for Núria Malats, head of the Genetic and Molecular Epidemiology Group at CNIO, to begin developing a personalized risk assessment application.
The tool will consider factors such as obesity, diabetes, pancreatitis, smoking, and alcohol consumption, integrating this information with genetic variation biomarkers – which slightly increase risk – and markers of methylation, the microbiome, and metabolome.
A recent CNIO study identified a genetic variant in the CTRB2 gene that increases the risk of developing the tumor, present in 17% of the population. While the risk conferred by this variant alone is not high, “when it appears alongside other factors, such as diabetes or pancreatitis, the risk could increase,” researchers explained.
Currently, there are no reliable methods for detecting pancreatic cancer before it becomes life-threatening, making the development of such tools a “most urgent” priority. The CNIO’s Epidemiology and Molecular Genetics Group is working on this through the PANCAID project – an international consortium of eight countries seeking to develop a blood test for early tumor detection.
NEW TREATMENT AVENUES
Malats’ group has also developed an algorithm that predicts the presence of metastasis based on images of the primary tumor. Utilizing Artificial Intelligence (AI), this technology could “assist surgeons and doctors in detecting metastasis,” ultimately improving patient quality of life.
Currently, only about 20% of patients are eligible for curative surgery, as the cancer is often detected after it has spread to other organs.
A significant challenge in treating pancreatic cancer is accurately determining whether metastasis has occurred. Many patients undergo surgery that ultimately doesn’t benefit them because metastasis was not detected early enough.
Alejo Efeyan, who leads the Cellular Metabolism and Signaling Group, is exploring ways to disrupt communication between the tumor and surrounding tissue, effectively cutting off the cancer’s support system.
“Pancreatic cancer cells are surrounded by numerous non-cancerous cells – supporting cells, blood vessels, nerves, immune cells… To weaken pancreatic cancer, we need to decipher the messages between all these cells and intercept the support the cancer cell receives. And then, strike with greater therapeutic efficacy,” Efeyan explained.
His team is investigating the link between obesity and pancreatic cancer, a connection that suggests “abnormal communication” between immune cells called macrophages and cancer cells. “We are close to deciphering, and then cutting, the chemical communication pathways,” he concluded.
