Pancreatic cancer remains one of the most challenging cancers to treat. One major reason is that many people are diagnosed at an advanced stage, when treatment options are more limited. In addition, even when treatments work at first, cancers can sometimes stop responding over time. This is why new approaches that aim to improve and prolong treatment effects deserve close attention.

A recently published study explored a new combination therapy that has shown encouraging results so far in laboratory studies and in mouse models of pancreatic cancer.

The researchers focused on pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic cancer. Many of these cancers are driven by changes in a gene called KRAS, which has long been difficult to target with drugs. In recent years, new medicines that block KRAS-related signals (including “RAS(ON) inhibitors”) have shown promising results, including improved survival in clinical trials. However, in both research models and in patients, tumours can eventually start growing again because the cancer becomes resistant to treatment.

To tackle this, the researchers tested a combination of three targeted treatments that block different “routes” cancer cells use to survive: a KRAS-pathway inhibitor (daraxonrasib), an EGFR/HER2 inhibitor (afatinib), and a STAT3-targeting drug (SD36). The goal was to make it harder for the cancer to “escape” by switching to another pathway.

In this study, the triple combination:

• Led to strong tumour shrinkage in multiple experimental models in mice
• Prevented the onset of treatment resistance in these models, meaning tumours did not return during long follow-up periods (in some experiments, mice stayed tumour-free for over 200 days)
• Appeared to be well-tolerated in mice, with limited side effects observed (for example, no significant weight loss was reported in the study)

Importantly, the approach also worked in patient-derived xenograft (PDX) models. This means tumour samples originally taken from patients were grown in immunodeficient mice to test how the treatment performs on real human tumour material in a living model.

While the findings are promising, it’s important to be clear: this research is still at an early stage.

So far, the treatment has only been tested in laboratory settings and in mice (including genetically engineered and orthotopic mouse models, and PDX tumours grown in immunodeficient mice). Before it can be offered as a treatment option for patients, many steps remain, including:

• Further safety testing
• Careful clinical trials in patients
• Adjustments to ensure the drug combination and doses are safe and effective for people

In other words, this is not yet a new treatment option, but rather a strong foundation on which future clinical research can build.

This study represents an important development for the pancreatic cancer community because it suggests that, at least in the models studied, it may be possible to achieve strong tumour regression while also delaying or preventing resistance. Researchers will now need to understand how this effect happens and whether similar strategies can be safely translated to people.

For patients, caregivers, and advocates, this kind of research reinforces why continued investment in science, collaboration, and clinical trials is essential. Progress may be slow, but studies like this show that meaningful advances are possible. At DiCE, we will continue to follow developments like this closely, sharing updates as the science moves forward, always with patients at the centre.

Author:

Laura Urena