According to the National Institute of Health, pancreatic cancer is considered as the third deadliest cancer to exist, with a recorded 51,980 deaths in 2025.
The notoriety that pancreatic cancer holds may soon disappear, however.
Led by Dr. Mariano Barbacid, scientists from the Spanish Cancer Research Centre just developed a treatment consisting of three drugs that eliminated a highly malignant form of pancreatic cancer in laboratory mice.
Best part about it? There are no side effects and tumor persistence, making it an extremely significant breakthrough in the field of pancreatic cancer research.
What is Pancreatic Cancer?
Just like with any form of cancer, pancreatic cancer occurs when an abnormal number of cells begin to proliferate in the pancreas which is located in the lower part of the stomach. The most common form of pancreatic cancer, pancreatic ductal adenocarcinoma (PDAC), happens when a mutation in the KRAS (Kirsten rat sarcoma virus oncogene) occurs. The compromised oncogene both initiates and maintains the signaling networks that create the tumors.
Prior to the recent study, efforts to create drugs that target these signaling pathways have been considered ineffective due to the high toxicities they possess. Unexpectedly in 2013, Dr. Kevan M. Shokat & his team discovered a small opening in the KRAS protein that house the inhibitors responsible for making the pancreatic tumors. This led to the creation of early RAS drugs such as sotorasib & adagrasib that target the KRAS G12C isoform.
A Decorated Individual: Dr. Mariano Barbacid
Born in Madrid, Spain, Dr. Mariano Barbacid is a prestigious molecular biochemist. In 1982, his discovery of the first human oncogene and its mutated version, H-ras, was integral of how human cancer develops. Additionally, Dr. Barbacid is also credited for isolating a TRK (Tropomyosin receptor kinase) oncogene which later became important for classifying them as the receptors of the NGF family of the neurotrophins. These are proteins that play a role in the central and peripheral nervous systems, facilitating the development, function, and survival of neurons.
Through Dr. Barbacid & his team’s recent study, they have made a new treatment that blocks most oncogenic KRAS isoforms as well as their normal counterpart.
Dr. Barbacid & his team work together to find treatment for pancreatic cancer.
(Credit: Embassy of Spain UK)
Newly Developed Treatment
Previous studies on pancreatic cancer showed that the RAF1 gene worked together with the epidermal growth factor receptor (EGFR). With this new study, Dr. Barbacid & co have discovered that targeting an additional KRAS signaling node, STAT3 (Signal transducer & activator of transcription) leads to a complete regression of PDAC tumor. Furthermore, they have applied these results in developing a treatment that is significantly less toxic than previous drugs. The treatment consists of three inhibitors: daraxonrasib, afatinib, and SD36.
For context, daraxonrasib is a recently developed RAS (ON) inhibitor that blocks ERK (Extracellular-regulated signal kinase) phosphorylation. Unfortunately, it does not stop the tumors from proliferating. Interestingly, when combined with afatinib (targets EGFR), STAT3 began to induce tumor resistance through phosphorylation. A newly experimental PROTAC (proteolysis targeting chimera) drug, SD36 was then added with the other two drugs to attack STAT3. The data was shocking.
The Results
The combination of daraxonrasib, afatinib, and SD36 showed that the PDAC cells completely died. Single & dual combinations either led to partial or no inhibition of cancer cell proliferation.
To validate their results, they implanted PDAC tumors onto laboratory mice. Again, single and dual-combination treatments did not lead to complete tumor regression as STAT3 continued to induce tumor resistance. When daraxonrasib, afatinib, and SD36 were combined, PDAC tumors in the laboratory mice were completely eliminated. More importantly, however, the mice tolerated the treatment well since their body parts (kidney, lungs, spleen) showed little to no signs of damage.
A Promising Future
Dr. Barbacid and his team have laid out the foundations for what could potentially be the cure for patients with pancreatic cancer. Of course, humans are more complex than laboratory rats. Nevertheless, the triple combination treatment showed promising results that could not only stop pancreatic cancer but also open up new possibilities for other prevalent cancers.