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10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
Almost every pancreatic tumour carries a KRAS mutation, and for the first time drugs against it work: daraxonrasib nearly doubled survival in previously treated disease in 2026. Pancreatic cancer has been the hardest common cancer to treat once advanced; that is what is starting to change.
Pancreatic ductal adenocarcinoma is defined by late presentation, a near-universal KRAS mutation (G12D about 40%, G12V about 32%, G12R about 16%, G12C 1 to 2%; 6 to 12% KRAS-wild-type with actionable fusions in NRG1, NTRK, ALK, or BRAF), a desmoplastic stroma that occupies most of the tumour, and an immunologically cold microenvironment. Surgery is the only cure and only ~20% of patients present resectable; five-year survival remains ~13% overall but exceeds 40% for resected patients who complete adjuvant mFOLFIRINOX.
For thirty years the story was chemotherapy: gemcitabine (1997), FOLFIRINOX (2011), gemcitabine/nab-paclitaxel (2013), adjuvant mFOLFIRINOX (PRODIGE 24, 2018), NALIRIFOX (2024), with olaparib maintenance for germline BRCA carriers (POLO, 2019) and zenocutuzumab for NRG1 fusions (2024) as the only biomarker-directed drugs. 2026 changed the trajectory. Optune Pax tumour treating fields were approved for locally advanced disease (PANOVA-3). Daraxonrasib, a pan-RAS(ON) inhibitor, nearly doubled overall survival in previously treated metastatic disease in RASolute 302 (13.2 vs 6.7 months, HR 0.40), presented in the ASCO 2026 plenary with simultaneous NEJM publication, and the FDA approved it on 26 August 2026 for metastatic disease after at least one systemic therapy or when multi-agent chemotherapy is unsuitable; no European or UK decision had been made by 24 September 2026. The G12D-selective zoldonrasib, combined with daraxonrasib or with chemotherapy, produced response rates never before seen in this disease.
| Setting | Approach | Guideline |
|---|---|---|
| High-risk surveillance | Annual MRI/MRCP or EUS for germline carriers and familial kindreds (CAPS/PRECEDE); germline testing for every diagnosed patient and first-degree relatives. | not mapped |
| Resectable / borderline | Neoadjuvant mFOLFIRINOX (borderline; increasingly resectable), surgery, then adjuvant mFOLFIRINOX to complete ~6 months (PRODIGE 24); gemcitabine/capecitabine if unfit. Chemoradiation selectively (PREOPANC). | not mapped |
| Locally advanced unresectable | FOLFIRINOX or gem/nab-paclitaxel; TTFields with gem/nab-paclitaxel (Optune Pax, 2026); SBRT or MR-guided ablative radiotherapy; IRE in selected centres; reassess for conversion surgery. | not mapped |
| Metastatic, first line | mFOLFIRINOX or NALIRIFOX (fit) or gemcitabine/nab-paclitaxel; olaparib maintenance if gBRCA after ≥16 weeks platinum; zenocutuzumab if NRG1 fusion; pembrolizumab if MSI-H; trials of RAS inhibitors + chemotherapy. | not mapped |
| Metastatic, second line | Daraxonrasib after one prior line (FDA approval 26 August 2026; RASolute 302: OS 13.2 vs 6.7 months, HR 0.40); otherwise switch backbone (gem/nab-pac after FOLFIRINOX, or liposomal irinotecan/5-FU after gemcitabine). No European or UK decision on daraxonrasib by 24 September 2026. | not mapped |
| Diagnosis and staging (UK pathway) | Pancreatic protocol CT of chest, abdomen and pelvis before any biliary drainage; FDG PET-CT for localised disease before treatment; EUS with tissue sampling when a diagnosis or node staging is needed; MRI for suspected liver metastases and laparoscopy with laparoscopic ultrasound before an attempted resection when small-volume spread is suspected; CA 19-9 at baseline; germline testing for every patient; decision by a specialist pancreatic multidisciplinary team. | not mapped |
| Nutrition and pancreatic enzyme replacement | Enteric-coated pancreatin for everyone with unresectable disease and consideration before and after resection; early enteral rather than parenteral nutrition after pancreatoduodenectomy; no fish oils for weight loss in unresectable disease; dietitian assessment for the weight loss, malabsorption and cachexia that affect most patients. | not mapped |
| Resectable or borderline: surgery first or chemotherapy first | About one in five pancreatic cancers can be removed at diagnosis (the OnCo record; Pancreatic Cancer UK says only a small number of people can have surgery), and the word the multidisciplinary team gives you decides the order. Resectable (no contact with the main arteries, no more than abutment of the veins, no spread): NICE NG85 says surgery first, and only consider chemotherapy before surgery within a clinical trial; the operation is usually a Whipple procedure for the head of the pancreas or a distal pancreatectomy for the body and tail, followed by six months of chemotherapy. Borderline resectable (the tumour touches a main vein or artery, so an operation straight away would probably leave cancer behind): chemotherapy first for two to four months, usually modified FOLFIRINOX, then restaging, with surgery about 6 to 8 weeks after chemotherapy if the disease has not spread; NICE NG85 also places this within a trial, and Cancer Research UK says your doctor may offer one because the best treatment is uncertain. In the Dutch PREOPANC trial, chemoradiotherapy before surgery improved five-year survival over surgery first (20.5% against 6.5%), most clearly for borderline disease; the record's open problems note the question is unresolved for resectable disease after PREOPANC-2, NORPACT-1 and Alliance A021806. Fitness matters as much as anatomy: only people well enough for a major operation are offered one, prehabilitation (exercise, nutrition, stopping smoking) is offered in some hospitals, and if jaundice needs relieving first a metal stent is placed. A second opinion from a specialist pancreatic centre is reasonable when the scan is read differently by different teams. | not mapped |