title: IGF1-R inhibition and liposomal doxorubicin: Progress in preclinical evaluation for the treatment of adrenocortical carcinoma.
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.
authors.affiliation: Endocrine Research Unit, Medizinische Klinik und Poliklinik IV, Klinikum der Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Beuschlein
authors.affiliation: Institute of Pharmaceutical Sciences, Department of Pharmaceutical Technology and Biopharmacy, Albert Ludwig University Freiburg, Freiburg, Germany.
authors.forename: Judith
authors.initials: J
authors.lastname: Jakoby
authors.affiliation: Endocrine Research Unit, Medizinische Klinik und Poliklinik IV, Klinikum der Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Mentz
authors.affiliation: Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: Gerard
authors.initials: G
authors.lastname: Zambetti
authors.affiliation: Endocrine Research Unit, Medizinische Klinik und Poliklinik IV, Klinikum der Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Sara
authors.initials: S
authors.lastname: Jung
authors.affiliation: Endocrine Research Unit, Medizinische Klinik und Poliklinik IV, Klinikum der Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Reincke
authors.affiliation: Institute of Pharmaceutical Sciences, Department of Pharmaceutical Technology and Biopharmacy, Albert Ludwig University Freiburg, Freiburg, Germany.
authors.forename: Regine
authors.initials: R
authors.lastname: Süss
authors.affiliation: Endocrine Research Unit, Medizinische Klinik und Poliklinik IV, Klinikum der Ludwig-Maximilians-Universität München, Munich, Germany. Electronic address: Constanze.Hantel@med.uni-muenchen.de.
authors.forename: Constanze
authors.initials: C
authors.lastname: Hantel
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018268:Adrenocortical Carcinoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008819:Mice, Nude; D010766:Phosphorylation / Q000187:drug effects; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis; D023041:Xenograft Model Antitumor Assays
chemical_list: D019394:Ki-67 Antigen; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D007335:Insulin-Like Growth Factor II; D004317:Doxorubicin; D017526:Receptor, IGF Type 1; D051057:Proto-Oncogene Proteins c-akt
keywords: Adrenocortical carcinoma; Caelyx(®); Immunoliposomes; Liposomal doxorubicin; MUC-1; NCI-H295R; SJ-ACC3