Losartan to loosen the stroma of pancreatic cancer before chemotherapy: a phase 3
A cheap blood pressure drug may soften the dense scar tissue around pancreatic tumours so chemotherapy and immune cells can get in. Early trials look encouraging.
Losartan inhibits angiotensin II and TGF-beta-driven fibrosis and, in mouse models, decompresses tumour vessels and improves drug delivery. A single-arm phase 2 (Massachusetts General Hospital) adding losartan to FOLFIRINOX and chemoradiation in locally advanced pancreatic cancer reported a high R0 resection rate, and a randomised phase 2 with added immunotherapy has followed. Losartan is off patent and costs a few dollars a month. The proposal is a publicly funded randomised phase 3 of losartan plus standard neoadjuvant therapy versus standard therapy alone in borderline resectable and locally advanced pancreatic cancer.
- No incentive to repurpose cheap drugs · Old, cheap drugs with anti-cancer signals never get the trials they need because no one profits from the result.
- Cold tumours and the immunosuppressive microenvironment · Most tumours keep the immune system out or asleep, so immunotherapy helps only a minority.