Nanoparticle albumin-bound (nab)-paclitaxel for the treatment of pancreas ductal adenocarcinoma

Article, Review English OPEN
Weekes, Colin ; Narayanan,Vignesh (2015)
  • Publisher: Dove Press
  • Journal: Gastrointestinal Cancer: Targets and Therapy (issn: 1179-9919)
  • Related identifiers: doi: 10.2147/GICTT.S55158
  • Subject: Diseases of the digestive system. Gastroenterology | Targets and Therapy [Gastrointestinal Cancer] | RC799-869 | RC254-282 | Neoplasms. Tumors. Oncology. Including cancer and carcinogens

Vignesh Narayanan,1 Colin D Weekes1,2 1Division of Medical Oncology, Department of Medicine, 2Developmental Therapeutics Program, University of Colorado Cancer Center, University of Colorado School of Medicine, Aurora, CO, USA Abstract: Pancreatic adenocarcinoma is a leading cause of cancer-related mortality worldwide, and surgical resection offers the only chance of cure. Since the majority of patients have unresectable disease at presentation, the emphasis has been on identifying effective chemotherapy regimens to prolong survival and control tumor burden. Gemcitabine has been the cornerstone of treatment ever since it was discovered to be an active agent in advanced pancreatic cancer nearly two decades ago, but the overall prognosis in patients with metastatic disease remains dismal. A dense fibrotic stroma around the tumor devoid of vasculature and the resultant hypoxic tumor microenvironment are implicated in the chemotherapy-resistant nature of this malignancy. In recent years, a growing body of literature has further elucidated several aspects of pancreatic tumor biology, such as its ability to utilize albumin from the peritumoral tissues to support its metabolic needs. High-pressure homogenization of paclitaxel with nanoparticle albumin results in the formation of soluble 130 nm complexes with albumin acting as the carrier for the otherwise hydrophobic paclitaxel. Once these complexes reach the tumor milieu, they act by depleting the tumor stroma. In addition, paclitaxel is also transported into the tumor cell along with albumin, where it then exerts its antineoplastic activity. Nanoparticle albumin-bound (nab)-paclitaxel also increases gemcitabine levels inside the tumor cells by inhibiting cytidine deaminase, the enzyme that degrades gemcitabine. This review focuses on proposed mechanisms of efficacy of nab-paclitaxel in pancreatic cancer and discusses the preclinical and clinical studies of relevance. Keywords: pancreatic adenocarcinoma, nab-paclitaxel, gemcitabine, SPARC, tumor stroma
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