# Losartan to loosen the stroma of pancreatic cancer before chemotherapy: a phase 3

Source: https://onco.cc/ideas/idea-reg-losartan-pancreatic-stroma/  
OnCo record `idea-reg-losartan-pancreatic-stroma` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Hypothesis: Adding losartan to neoadjuvant chemotherapy increases the R0 resection rate by at least 15 absolute percentage points and improves overall survival in locally advanced pancreatic cancer.
- Rationale: Stromal desmoplasia is the defining obstacle in pancreatic cancer and many expensive stroma-targeting agents have failed; losartan's mechanism is supported by imaging and tissue data in patients, and its safety is well known.
- Proposed test: Randomised phase 3 of roughly 400 patients with R0 resection rate and OS endpoints, with imaging biomarkers of tumour perfusion in a sub-study.
- Maturity: early-clinical
- Actor: research

## Sources

- Bottleneck evidence (No incentive to repurpose cheap drugs): Pantziarka et al., The Repurposing Drugs in Oncology (ReDO) Project (ecancer 2014): https://doi.org/10.3332/ecancer.2014.442

## Connected records

- cancers: [Locally advanced unresectable pancreatic ductal adenocarcinoma](https://onco.cc/cancers/locally-advanced-pdac/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/)
- institutions: [Massachusetts General Hospital Cancer Center](https://onco.cc/institutions/mgh/)
- pathways: [Epithelial-mesenchymal transition & drug efflux](https://onco.cc/pathways/emt/)
- bottlenecks: [Cold tumours and the immunosuppressive microenvironment](https://onco.cc/bottlenecks/b-tme-immunosuppression/), [No incentive to repurpose cheap drugs](https://onco.cc/bottlenecks/b-generic-repurposing/)
- key papers: [The Repurposing Drugs in Oncology (ReDO) Project](https://onco.cc/key-papers/paper-pantziarka-ecancermedicalscience/)

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