Scientists crack an "undruggable" pancreatic cancer target and nearly double survival

Researchers at Stanford University and MIT have developed a new peptide-based inhibitor that targets the KRAS-G12D mutation, which drives about 95% of pancreatic cancers and has been viewed for decades as "undruggable". Phase-1 results outlined by Science Daily show median survival in patients who had not responded to chemotherapy approximately doubled.

KRAS is a protein that controls cell-growth signalling. When it is mutated, cells multiply uncontrollably. Because the surface of KRAS has no pocket wide enough to bind a drug in the classical way, the protein has been called "undruggable".

Dr Eunhee Park, lead investigator at Stanford's oncology department, told Science Daily: "After a decade of work we have a peptide that really binds KRAS-G12D and crosses out of the bloodstream into tissue well enough." The cyclic ring of the molecule, named SP-241, was designed to lock onto short-lived clefts on the KRAS surface.

The phase-1 trial enrolled 60 metastatic pancreatic adenocarcinoma patients who had failed two or three lines of chemotherapy. Median progression-free survival rose from a control benchmark of 2.1 months to 5.8 months with SP-241; median overall survival rose from 7 months to 13.2 months.

The clinical cohort is small and confirmation depends on a randomised phase-3 trial, but the Stanford team said next-generation variants targeting other KRAS mutations are already being tested. The MIT team has mapped binding profiles for KRAS-G12C and G12V mutations seen in lung and colon cancers.

On side effects, the most common were grade 1-2 rash and transient thrombocytopenia. Five patients developed immune-mediated hepatitis, which resolved when treatment was stopped. Clinicians describe the profile as comparable to existing targeted therapies.

Daniel Liu, professor of bioengineering at MIT, told Science Daily: "This is not just about pancreatic cancer — it opens up a map for drugging the KRAS family. We expect phase-1 data for lung and colon over the next few years."

In the United States, pancreatic cancer caused around 67,000 new cases and 52,000 deaths in 2025, with a five-year survival rate of about 13%. If SP-241 is approved and the effect is confirmed in randomised trials, the clinical impact could rank among the largest in the past 30 years.

Cyclophos, the biotech that originated the drug, plans to begin phase-2 trials in the middle of this year and to complete phase 3 in 2027. A submission to the US Food and Drug Administration's Accelerated Approval pathway is expected; the European Medicines Agency has indicated interest in a parallel review.

This article is not medical advice. Pancreatic cancer patients should ask their oncologists about eligibility for ongoing SP-241 clinical trials and discuss treatment options with their multidisciplinary clinical team.