Blood Pressure Drug May Help Locally Advanced Pancreatic Cancer Patients

Since surgical excision of tumor tissue is now the only option for the majority of pancreatic cancer patients, the disease is extremely fatal. Treatment options are few once the malignancy has left the pancreas.

A promising combination treatment regimen was found in a recent phase II clinical trial run by doctors at Massachusetts General Hospital (MGH) for patients with locally progressed pancreatic cancer, which means that the disease has only migrated to adjacent tissue. The trial’s researchers have now identified plausible processes that could account for the therapeutic results.

Losartan is a blood pressure medication, and the combination therapy FOLFIRINOX (folinic acid, fluorouracil, irinotecan, and oxaliplatin) is a chemotherapy cocktail, followed by chemoradiation. Before a patient has surgery to remove any remaining pancreatic tumors, the therapy is intended to treat as much cancer as possible. The phase II clinical trial showed that it is effective in achieving this.

Researchers examined blood and tissue samples from patients receiving this and other treatments for locally advanced pancreatic cancer in this most recent study, which was published in Clinical Cancer Research. The researchers discovered that FFX+CRT enhanced the expression of genes related to blood vessel normalization, immune cell migration, and maturation.

Inhibiting immunosuppression and lowering the expression of genes that encourage tumor cell migration into healthy tissue were two effects of Losartan+FFX+CRT. Additionally, losartan caused alterations in the blood levels of several molecules related to immune function and healthy blood vessels. Last but not least, tumor tissue from patients receiving Losartan+FFX+CRT treatment showed a reduction in immune-suppressing cells and an increase in immune cells vital for eliminating malignant or virally contaminated cells.

“Our findings suggest that losartan may potentiate the benefit of FFX+CRT by reducing tumor invasion and immunosuppression. Thus, our results are important because they would not only reveal how losartan may synergize with emerging cytotoxic regimens, but also provide valuable information for overcoming resistance to immunotherapy—such as immune checkpoint blockers—that can occur in pancreatic cancer,” says a senior author Rakesh K. Jain, Ph.D., director of the E.L. Steele Laboratories for Tumour Biology at MGH and the Andrew Werk Cook Professor of Radiation Oncology at Harvard Medical School.

Interestingly, Jain and his colleagues found that blood levels of a molecule called soluble Tie2 increased over time in patients treated with losartan+FFX+CRT who experienced only a partial or poor response. Therefore, an increase in soluble Tie2 (which is involved in new blood vessel formation) could be an indication of tumor progression.

“Inspired by our published studies on the benefit of adding losartan, several clinical trials in patients with pancreatic cancer are currently evaluating the effectiveness of adding losartan to different cytotoxic treatment regimens or cytotoxics plus immunotherapy,” says Jain. “When completed, these clinical trials will indicate whether Losartan, when combined with different therapies, can improve the treatment response and long-term survival of patients with pancreatic cancer.”

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