Nab-Paclitaxel Plus S-1 Shows Increased Antitumor Activity in Patient-Derived Pancreatic Cancer Xenograft Mouse Models.
OBJECTIVE
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.
From the Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Jian-Ang
JA
Li
Xue-Feng
XF
Xu
Xu
X
Han
Yuan
Y
Fang
Chen-Ye
CY
Shi
Da-Yong
DY
Jin
Wen-Hui
WH
Lou
D000418:Albumins / Q000008:administration & dosage; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000378:metabolism; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008819:Mice, Nude; D009962:Orotate Phosphoribosyltransferase / Q000378:metabolism; D010094:Oxonic Acid / Q000008:administration & dosage; D017239:Paclitaxel / Q000008:administration & dosage; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011897:Random Allocation; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D005641:Tegafur / Q000008:administration & dosage; D013940:Thymidylate Synthase / Q000378:metabolism; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
D000418:Albumins; D014408:Biomarkers, Tumor; D024042:Collagen Type I; D042943:Dihydrouracil Dehydrogenase (NADP); D004338:Drug Combinations; D009962:Orotate Phosphoribosyltransferase; D010094:Oxonic Acid; D017239:Paclitaxel; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D018719:Erb-b2 Receptor Tyrosine Kinases; D005641:Tegafur; D013940:Thymidylate Synthase; C520255:130-nm albumin-bound paclitaxel; C079198:S 1 (combination)