Pancreatic cancer just met its match
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Pancreatic cancer just met its match<br>A disease that was once a death sentence is increasingly treatable
Ruxandra Teslo and Works in Progress<br>May 12, 2026
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For most of the last half-century, a diagnosis of metastatic pancreatic cancer was a death sentence. In December 2025, former Nebraska Senator Ben Sasse announced he had been diagnosed with stage four pancreatic cancer that had spread to his lungs, liver and other organs, and was given three to four months to live from the time of diagnosis. With little to lose, he enrolled in a clinical trial for an experimental drug. Four months later, he reported a 76 percent reduction in tumor volume, describing the drug, daraxonrasib, as a ‘miracle’. His face, ravaged by a severe skin rash from the treatment, told a more complicated story. Yet he was alive and grateful to be able to talk to his family.<br>A few days after Sasse’s interview, in April 2026, Revolution Medicines announced Phase 3 trial results for daraxonrasib showing the drug had roughly doubled survival in patients with metastatic pancreatic cancer compared to standard chemotherapy. For a disease where median survival has long been measured in months and where little had changed for decades, that result represents a genuine turning point.<br>But the significance extends beyond pancreatic cancer. Daraxonrasib is among the first drugs in an emerging generation designed to target RAS, a protein implicated in roughly a quarter of all human cancers and long considered beyond reach, in all its mutant forms. And it belongs to a broader class of medicines, molecular glues, that are beginning to show what becomes possible when drugs no longer depend on finding a ready-made pocket in their target. Several compounds in this class are now in clinical development, each probing a different protein that previous generations of drugs could not touch.<br>Pancreatic cancer: a tough nut to crack
Pancreatic cancer has the highest mortality rate of all major cancers. Although its five-year survival rate has improved from roughly 4 percent in the mid-1990s to around 13 percent today, it remains among the deadliest of all cancer types.<br>Survival is so poor partially because pancreatic cancer is typically diagnosed late: the pancreas sits deep in the abdomen, symptoms are vague and late to appear, and by the time most patients are diagnosed, the cancer has already spread. This feature has earned pancreatic cancer the name ‘silent killer’. Metastatic cases, where the tumor has already spread to other organs, represent more than half of all new diagnoses. For these patients in particular there has been minimal improvement in outcomes over recent decades, with just 2 to 3 percent still alive five years after their diagnosis.<br>For decades, no fundamentally new and effective treatments for metastatic cancer emerged. That changed in 2011, when a wave of innovation began transforming the field. At the heart of this renaissance are immunotherapies: drugs that harness the body’s own immune system to fight cancer. Among them are checkpoint inhibitors, which work by releasing the natural brakes on immune activity, and CAR-T therapies, a new class of anti-cancer wonder treatments which engineer a patient’s own immune cells into precision cancer-fighting weapons.<br>These treatments have redrawn the boundaries of what is possible in oncology. In metastatic melanoma (the most serious type of skin cancer), immunotherapy has produced results once thought unimaginable: from only 25 percent survival after one year twenty years ago to 50 percent survival after 10 years now. Unfortunately, metastatic pancreatic cancer is particularly good at protecting itself against immune attack and has thus remained beyond the reach of this newer wave of drugs.<br>Pancreatic tumors build a shield around themselves to evade immune attack. They are surrounded by a dense, scar-like layer of tissue that physically blocks a patient’s immune cells from entering the tumor. As a result, checkpoint inhibitors, which work by reactivating immune responses, often have little effect. CAR-T therapies also struggle to penetrate this physical barrier. Even when immune cells do manage to get inside, the tumor creates a hostile environment that weakens them. It does this by attracting suppressive immune cells, including regulatory T cells, myeloid-derived suppressor cells, and tumor-associated macrophages, and by releasing molecules that dampen immune function.
Pancreatic cancers surround themselves with a physical barrier that helps them escape immune attack. Adapted from here. PDAC = pancreatic ductal adenocarcinoma; TAM = tumor associated macrophage; CAF = cancer associated fibroblast.<br>There is a further problem that compounds this. Immunotherapy tends to work best against genetically ‘noisy’ tumors: cancers with many mutations that generate abnormal surface proteins, known as...