Nab-Paclitaxel Plus S-1 Shows Increased Antitumor Activity in Patient-Derived Pancreatic Cancer Xenograft Mouse Models.

Abstract

OBJECTIVES:

To investigate the antitumor activity of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) plus S-1 in patient-derived pancreatic cancer xenograft mouse models and to explore biomarkers that could predict drug efficacy.

METHODS:

Ten patient-derived xenograft models were established. The third-generation tumor-bearing mice were randomized into 4 treatment groups: (1) control; (2) S-1; (3) nab-paclitaxel; (4) S-1 plus nab-paclitaxel. Resected tumors were tested by immunohistochemistry for the expression of thymidylate synthase, orotate phosphoribosyltransferase (OPRT), dihydropyrimidine dehydrogenase (DPD), secreted protein that is acidic and rich in cysteine, human epidermal growth factor receptor 2 (HER2), collagen-1, and CD31.

RESULTS:

Tumor growth inhibition of the S-1 group, nab-paclitaxel group, and combination group was 69.52%, 86.63%, 103.56%, respectively (P < 0.05). The efficacy of S-1 is better in thymidylate synthase-negative, OPRT-positive, and DPD-negative tumors. The efficacy of nab-paclitaxel is better in HER2-positive tumors. Collagen-1 was decreased and CD31 was increased in tumors treated with nab-paclitaxel and S-1 plus nab-paclitaxel compared with control or S-1.

CONCLUSIONS:

This preclinical study showed that S-1 plus nab-paclitaxel exerted significantly better antitumor activity than S-1 or nab-paclitaxel alone. Thymidylate synthase, OPRT, and DPD were possibly biomarkers of S-1 and HER2 of nab-paclitaxel.

• Authors: Jian-Ang Li, Xue-Feng Xu, Xu Han, Yuan Fang, Chen-Ye Shi, Da-Yong Jin, Wen-Hui Lou
• Journal: Pancreas (Pancreas) Vol. 45 Issue 3 Pg. 425-33 (Mar 2016) ISSN: 1536-4828 [Electronic] United States
• PMID: 26495780 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 130-nm albumin-bound paclitaxel
• Albumins
• Biomarkers, Tumor
• Collagen Type I
• Drug Combinations
• Platelet Endothelial Cell Adhesion Molecule-1
• S 1 (combination)
• Tegafur
• Oxonic Acid
• Dihydrouracil Dehydrogenase (NADP)
• Thymidylate Synthase
• Orotate Phosphoribosyltransferase
• Receptor, ErbB-2
• Paclitaxel

Topics

• Albumins (administration & dosage)
• Animals
• Antineoplastic Combined Chemotherapy Protocols (pharmacology)
• Biomarkers, Tumor (metabolism)
• Collagen Type I (metabolism)
• Dihydrouracil Dehydrogenase (NADP) (metabolism)
• Drug Combinations
• Female
• Humans
• Immunohistochemistry
• Mice, Nude
• Orotate Phosphoribosyltransferase (metabolism)
• Oxonic Acid (administration & dosage)
• Paclitaxel (administration & dosage)
• Pancreas (drug effects, metabolism, pathology)
• Pancreatic Neoplasms (drug therapy)
• Platelet Endothelial Cell Adhesion Molecule-1 (metabolism)
• Random Allocation
• Receptor, ErbB-2 (metabolism)
• Tegafur (administration & dosage)
• Thymidylate Synthase (metabolism)
• Treatment Outcome
• Xenograft Model Antitumor Assays