Preclinical investigation of nanoparticle albumin-bound paclitaxel as a potential treatment for adrenocortical cancer

Ann Surg. 2012 Jan;255(1):140-6. doi: 10.1097/SLA.0b013e3182402d21.


Background: Traditional drug discovery methods have a limited role in rare cancers. We hypothesized that molecular technology including gene expression profiling could expose novel targets for therapy in adrenocortical carcinoma (ACC), a rare and lethal cancer. SPARC (secreted protein acidic rich in cysteine) is an albumin-binding matrix-associated protein that is proposed to act as a mechanism for the increased efficacy of a nanoparticle albumin-bound preparation of the antimicrotubular drug Paclitaxel (nab-paclitaxel).

Methods: The transcriptomes of 19 ACC tumors and 4 normal adrenal glands were profiled on Affymetrix U133 Plus2 expression microarrays to identify genes representing potential therapeutic targets. Immunohistochemical analysis for target proteins was performed on 10 ACC, 6 benign adenomas, and 1 normal adrenal gland. Agents known to inhibit selected targets were tested in comparison with mitotane in the 2 ACC cell lines (H295R and SW-13) in vitro and in mouse xenografts.

Results: SPARC expression is increased in ACC samples by 1.56 ± 0.44 (μ ± SD) fold. Paclitaxel and nab-paclitaxel show in vitro inhibition of H295R and SW-13 cells at IC50 concentrations of 0.33 μM and 0.0078 μM for paclitaxel and 0.35 μM and 0.0087 μM for nab-paclitaxel compared with mitotane concentrations of 15.9 μM and 46.4 μM. In vivo nab-paclitaxel treatment shows a greater decrease in tumor weight in both xenograft models than mitotane.

Conclusions: Biological insights garnered through expression profiling of ACC tumors suggest further investigation into the use of nab-paclitaxel for the treatment of ACC.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Neoplasms / genetics*
  • Adrenal Cortex Neoplasms / pathology*
  • Adrenocortical Adenoma / genetics*
  • Adrenocortical Adenoma / pathology*
  • Albumin-Bound Paclitaxel
  • Albumins / pharmacology
  • Animals
  • Antineoplastic Agents, Hormonal / pharmacology
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Drug Delivery Systems / methods*
  • Gene Expression Profiling*
  • Humans
  • Mice
  • Mitotane / pharmacology
  • Nanoparticles
  • Neoplasm Transplantation / pathology
  • Paclitaxel / pharmacology*
  • Tumor Burden
  • Xenograft Model Antitumor Assays


  • Albumin-Bound Paclitaxel
  • Albumins
  • Antineoplastic Agents, Hormonal
  • Antineoplastic Agents, Phytogenic
  • Mitotane
  • Paclitaxel