IGF1-R inhibition and liposomal doxorubicin: Progress in preclinical evaluation for the treatment of adrenocortical carcinoma

Mol Cell Endocrinol. 2016 Jun 15:428:82-8. doi: 10.1016/j.mce.2016.03.023. Epub 2016 Mar 17.

Abstract

Adrenocortical carcinoma (ACC) is a tumor with poor prognosis and limited therapeutic options. Therefore, in addition to multi-chemotherapeutic regimens IGF-1 receptor (IGF-1R) targeting approaches have been evaluated including immunoliposomal (IL) preparations utilizing an IGF-1R inhibiting antibody. In the current study, we extended our experiments by long-term treatment regimens in the classical adrenocortical NCIH295R xenograft model as well as by short-term experiments in two novel xenograft models, which all displayed different levels of IGF-1R and IGF-2 expression. Interestingly, these experiments reveal sub-group dependent differences in therapeutic outcome, reflecting clinical observations and indicate, thus, that implementation of this panel of tumor models might be helpful for clinical translation of novel therapeutic regimens in the future.

Keywords: Adrenocortical carcinoma; Caelyx(®); Immunoliposomes; Liposomal doxorubicin; MUC-1; NCI-H295R; SJ-ACC3.

MeSH terms

  • Adrenal Cortex Neoplasms / drug therapy*
  • Adrenal Cortex Neoplasms / genetics
  • Adrenal Cortex Neoplasms / pathology
  • Adrenocortical Carcinoma / drug therapy*
  • Adrenocortical Carcinoma / genetics
  • Adrenocortical Carcinoma / pathology
  • Animals
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Doxorubicin / adverse effects
  • Doxorubicin / analogs & derivatives*
  • Doxorubicin / pharmacology
  • Doxorubicin / therapeutic use
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Insulin-Like Growth Factor II / metabolism
  • Ki-67 Antigen / metabolism
  • Mice, Nude
  • Phosphorylation / drug effects
  • Polyethylene Glycols / adverse effects
  • Polyethylene Glycols / pharmacology
  • Polyethylene Glycols / therapeutic use
  • Proto-Oncogene Proteins c-akt / metabolism
  • Real-Time Polymerase Chain Reaction
  • Receptor, IGF Type 1 / antagonists & inhibitors*
  • Receptor, IGF Type 1 / genetics
  • Receptor, IGF Type 1 / metabolism
  • Survival Analysis
  • Xenograft Model Antitumor Assays

Substances

  • Ki-67 Antigen
  • liposomal doxorubicin
  • Polyethylene Glycols
  • Insulin-Like Growth Factor II
  • Doxorubicin
  • Receptor, IGF Type 1
  • Proto-Oncogene Proteins c-akt