Paricalcitol Clears 36-Patient Pancreatic Cancer Trial, Though 42% on Oral Doses Had Hypercalcemia
Updated
Updated · Nature.com · May 25
Paricalcitol Clears 36-Patient Pancreatic Cancer Trial, Though 42% on Oral Doses Had Hypercalcemia
3 articles · Updated · Nature.com · May 25
Thirty-six patients with metastatic pancreatic cancer were randomized to gemcitabine plus nab-paclitaxel with placebo, intravenous paricalcitol or oral paricalcitol, and the VDR agonist was judged safe enough to combine with first-line chemotherapy.
Five patients in the oral paricalcitol arm—42% of that group—developed grade 2 to 4 hypercalcemia and needed dose reductions, marking the main safety signal in the run-in phase study.
On-treatment biopsies in the paricalcitol arms showed fewer αSMA-positive fibroblasts, altered fibroblast VDR activation signatures, and denser CD8-positive T-cell presence near tumor cells, consistent with tumor-microenvironment remodeling.
Baseline VDR expression varied across patients and cell types, and higher VDR expression predicted tumor response only in the paricalcitol-treated groups, suggesting a potential biomarker for selecting patients.
The findings support further testing of stromal-targeting vitamin D receptor agonists in pancreatic cancer, where resistance to chemotherapy is closely tied to the tumor microenvironment.
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Transforming Pancreatic Cancer Treatment: Paricalcitol’s Impact on Tumor Stroma and Combination Therapy Strategies
Overview
A major breakthrough in metastatic pancreatic cancer treatment was recently published, led by Dana-Farber Cancer Institute researchers and based on a concept from the Salk Institute. This new strategy targets the vitamin D receptor (VDR) to change the tumor microenvironment, which is a key reason pancreatic cancer resists standard therapies. The study focused on paricalcitol, a synthetic vitamin D analog, showing that activating VDR can remodel the dense stroma around tumors. This approach aims to make chemotherapy more effective, offering hope for better outcomes in a cancer that is usually very hard to treat.