Temsirolimus combined with cisplatin or bevacizumab is active in osteosarcoma models.

Mammalian target of rapamycin (mTOR) is a new promising oncological target. However, most clinical studies reported only modest antitumor activity during mTOR-targeted monotherapies, including studies in osteosarcomas, emphasizing a need for improvement. We hypothesized that the combination with rationally selected other therapeutic agents may improve response.

IGF signaling pathway analysis of osteosarcomas reveals the prognostic value of pAKT localization.

Aim: The aim of this study was to examine the expression of the IGF signaling pathway components in osteosarcoma samples before and after chemotherapy with special emphasis on their prognostic value.

Materials & Methods: Tumor material and follow-up data of 58 osteosarcoma patients were analyzed. Immunohistochemical staining was carried out to identify proteins related to the IGF pathway.

Simultaneous targeting of insulin-like growth factor-1 receptor and anaplastic lymphoma kinase in embryonal and alveolar rhabdomyosarcoma: a rational choice.

Background: Rhabdomyosarcoma (RMS) is an aggressive soft tissue tumour mainly affecting children and adolescents. Since survival of high-risk patients remains poor, new treatment options are awaited. The aim of this study is to investigate anaplastic lymphoma kinase (ALK) and insulin-like growth factor-1 receptor (IGF-1R) as potential therapeutic targets in RMS.

The strength of small: improved targeting of insulin-like growth factor-1 receptor (IGF-1R) with F(ab')₂-R1507 fragments in Ewing sarcomas.

Purpose: To investigate whether F(ab')₂-fragments of the monoclonal Insulin-like Growth Factor-1 Receptor (IGF-1R) antibody R1507 (F(ab')₂-R1507) can successfully target IGF-1R in Ewing sarcomas (ES).

Materials And Methods: BALB/c nude mice were subcutaneously implanted with IGF-1R-expressing human ES xenografts (EW-5 and EW-8) which previously showed heterogeneous or no uptake of indium-111-labelled R1507 IgG ((111)In-R1507), respectively. Mice were injected with (111)In-F(ab')₂-R1507 or (111)In-R1507 as a reference.

Expression and clinical relevance of MET and ALK in Ewing sarcomas.

Because novel therapeutic options are limited in Ewing sarcomas (ES), we investigated the expression, genetic aberrations and clinical relevance of MET and anaplastic lymphoma kinase (ALK) in ES and determined the relevance of targeting these receptors. MET and ALK protein expression was determined immunohistochemically in 31 (50 samples) and 36 (59 samples) ES patients, respectively. Samples included primary tumors, postchemotherapy resections, metastases and relapses.

Anaplastic lymphoma kinase aberrations in rhabdomyosarcoma: clinical and prognostic implications.

Purpose: The aim of this study is to investigate anaplastic lymphoma kinase (ALK) protein expression and underlying genetic aberrations in rhabdomyosarcoma (RMS), with special attention to clinical and prognostic implications.

Patients And Methods: A total of 189 paraffin-embedded RMS tumor specimens from 145 patients were collected on tissue microarray. ALK protein expression was evaluated by immunohistochemistry.

Predicting IGF-1R therapy response in bone sarcomas: immuno-SPECT imaging with radiolabeled R1507.

Purpose: To investigate whether indium-111-labeled R1507 ((111)In-R1507) immuno-SPECT (single-photon emission computed tomography), a novel noninvasive, in vivo screening method to visualize membranous insulin-like growth factor 1 receptor (IGF-1R) expression and accessibility, can be used to predict IGF-1R treatment (R1507) response in bone sarcomas.

Experimental Design: BALB/c nude mice were subcutaneously implanted with IGF-1R-expressing human bone sarcoma xenografts (OS-1, EW-5, and EW-8) which showed high, modest, or no response, respectively, to R1507, a monoclonal antibody targeting the extracellular domain of IGF-1R. An IGF-1R-negative tumor (OS-33), unresponsive to IGF-1R inhibitors, was examined as well.