Scientists have eliminated pancreatic cancer entirely for the first time, in mice. Researchers at Spain’s National Cancer Research Centre (CNIO), led by Mariano Barbacid, have eliminated pancreatic cancer in mice for the first time, according to new findings that address one of the disease’s biggest treatment challenges, which is drug resistance.
The study focused on pancreatic ductal adenocarcinoma (known as PDAC), the most common and aggressive form of pancreatic cancer. For decades, treatment options showed little progress beyond conventional chemotherapy. In 2021, the first drugs targeting KRAS, a gene mutated in around 90 per cent of pancreatic cancer cases, were approved.
However, their clinical benefit has been minor, as tumours frequently develop resistance within months following treatment. Barbacid and his team sought to overcome this limitation by targeting the KRAS signalling pathway at three separate points simultaneously, rather than inhibiting a single molecule. This approach was designed to make it significantly harder for cancer cells to bypass the treatment. Using three genetically engineered mouse models, the researchers eliminated three key molecules in the KRAS pathway. In these models, the tumours disappeared permanently.
The team then applied the same principle in a therapeutic setting by testing a triple-combination treatment that included an experimental drug previously used in lung cancer, a protein degrader, and an additional targeted agent. Across the mice models, the combination therapy led to the complete disappearance of tumours in all and prevented the emergence of resistant disease.
Whilst further research will be needed to determine whether the strategy can be translated into human treatments, the results represent a notable advance in pancreatic cancer research. Mice and humans share 85-97.5% of DNA, so although this treatment can’t be applied to patients yet, the future certainly looks promising.
Given the aggressive nature of pancreatic cancer, as well as difficulty in establishing treatment resistance, the CNIO’s findings show evidence that multi-targeted strategies may provide a more durable path forward for cancer treatments.
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