Article

Targeting CD99 in association with doxorubicin: an effective combined treatment for Ewing's sarcoma.

Laboratorio di Ricerca Oncologica, Istituti Ortopedici Rizzoli, Bologna 40136, Italy.
European Journal of Cancer (Impact Factor: 5.06). 02/2006; 42(1):91-6. DOI: 10.1016/j.ejca.2005.09.015
Source: PubMed

ABSTRACT CD99 is a 32kDa surface glycoprotein that is involved in the migration of leukocytes, cell-cell adhesion and apoptosis of T cells and Ewing's sarcoma (ES) cells, two cell types with a high level of CD99 expression. Engagement of the molecule induces a rapid death signal that appears to be related to the level of expression of this antigen. The rapid apoptosis induced by agonistic anti-CD99 monoclonal antibodies is of clinical interest in ES, a tumour for which no new drugs have been described as clearly effective in the last 10 years. In this study, we show that an anti-CD99 monoclonal antibody can be used to advantage in association with doxorubicin. Striking effectiveness was observed against local tumours and metastases. No remarkably toxic effects of anti-CD99 monoclonal antibody were found in bone marrow against blood precursors. These results provide the necessary rationale and support for a novel modality of therapeutic intervention, which may have application in the care of patients with ES.

0 Bookmarks
 · 
100 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Although Ewing sarcoma represents a rare malignancy of childhood and adolescence, it has attracted the attention of an increasing number of excellent researchers. With a tumor-specific EWS-ETS translocation coding for a transcription factor, which obviously profoundly modifies the intracellular signaling network, this rare malignancy opens insights in pathological gene and protein regulation. Despite decades of basic and translational research, clinical improvement has not yet been modulated by novel targeted therapies, but is produced by well-designed multimodal treatments. By using these multimodal treatment approaches, which always include chemotherapy and local treatment, the prognosis has been improved by up to 70%. For more than 10 years, the survival curves have plateaued at a relatively high level. However, a 30% relapse rate is still unacceptably high, considering that the prognosis after relapse is fatal for most patients. Therefore, novel treatment approaches are urgently required. This article provides an overview of the Ewing sarcoma research of the past few years; while not claiming to be complete, it offers a view on putative strategies with translational potential.
    Future Oncology 07/2010; 6(7):1155-62. · 3.20 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The Ewing sarcoma family of tumors (ESFT) is defined by cell surface expression of CD99 and a translocation involving EWS and an ETS partner. Cytotoxic chemotherapy remains the benchmark of first- and second-line therapy, and although the majority of patients with localized disease are cured, almost one third of patients relapse or progress from their disease. Moreover, cure remains elusive in most patients who present with distant metastases. In recent years, the ESFT literature has been dominated by reports of attempts at modulating the insulin-like growth factor (IGF) receptor (IGFR). Unfortunately, three phase II studies examining inhibiting antibodies to IGFR-1 published disappointing results. Whether these results were due to failure to modulate the pathway or other limitations in study design and/or patient selection remain unclear. Other novel strategies currently being investigated in ESFT include tyrosine kinase, mammalian target of rapamycin (mTOR), and poly(ADP-ribose) polymerase (PARP) inhibitors.
    Paediatric Drugs 06/2013; · 1.72 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Rhabdomyosarcomas (RMS) are a heterogeneous group of tumors that share features of skeletal myogenesis and represent the most common pediatric soft tissue sarcoma. Even though significant advances have been achieved in RMS treatment, prognosis remains very poor for many patients. Several elements of the Insulin-like Growth Factor (IGF) pathway are involved in sarcomas, including RMS. The IGF2 ligand is highly expressed in most, if not all, RMS, and frequent overexpression of the receptor IGF1R is also found. This is confirmed here through mining expression profiling data of a large series of RMS samples. IGF signaling is implicated in the genesis, growth, proliferation, and metastasis of RMS. Blockade of this pathway is therefore a potential therapeutic strategy for the treatment of RMS. In this paper we examine the biological rationale for targeting the IGF pathway in RMS as well as the current associated preclinical and clinical experience.
    Sarcoma 01/2011; 2011:209736.

Full-text (2 Sources)

View
64 Downloads
Available from
May 19, 2014