Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuroblastoma is the most common extra-cranial malignancy of childhood, with the highest incidence in children younger than 4 years. The prognosis depends on many factors, such as age at diagnosis, stage of disease and molecular genetic subtype. More than 50% of children who present with the disease are deemed to have high-risk neuroblastoma. The standard therapy for children with high-risk neuroblastoma consists of intensive chemotherapy, surgery, radiotherapy, myeloablative consolidation with autologous haematopoietic stem cell rescue followed by the treatment of minimal residual disease with 13-cis-retinoic acid. Unfortunately, more than half of the patients relapse regardless of the treatment intensity. Combined therapy with monoclonal antibodies (anti-GD2), intravenous interleukin-2 (Il-2), intravenous granulocyte-macrophage colony-stimulating factor (GM-CSF) and oral 13-cis-retinoic acid have been proved to be effective in some randomised trials. A better understanding of the underlying immunological processes in therapy with anti-GD2 antibodies will allow its success to be evaluated more accurately and direct future endeavours. Nevertheless, the long-term benefit of this treatment approach needs to be established.
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PMID:Evidence for the efficacy of immunotherapy in children with high-risk neuroblastoma. 2770 4

Neuroblastoma (NB) is a pediatric cancer of the sympathetic nervous system which accounts for 8% of childhood cancers. Most NBs express high levels of the disialoganglioside GD2. Several antibodies have been developed to target GD2 on NB, including the human/mouse chimeric antibody ch14.18, known as dinutuximab. Dinutuximab used in combination with granulocyte-macrophage colony-stimulating factor, interleukin-2, and isotretinoin (13-cis-retinoic acid) has a US Food and Drug Administration (FDA)-registered indication for treating high-risk NB patients who achieved at least a partial response to prior first-line multi-agent, multimodality therapy. The FDA registration resulted from a prospective randomized trial assessing the benefit of adding dinutuximab + cytokines to post-myeloablative maintenance therapy for high-risk NB. Dinutuximab has also shown promising antitumor activity when combined with temozolomide and irinotecan in treating NB progressive disease. Clinical activity of dinutuximab and other GD2-targeted therapies relies on the presence of the GD2 antigen on NB cells. Some NBs have been reported as GD2 low or negative, and such tumor cells could be nonresponsive to anti-GD2 therapy. As dinutuximab relies on complement and effector cells to mediate NB killing, factors affecting those components of patient response may also decrease dinutuximab effectiveness. This review summarizes the development of GD2 antibody-targeted therapy, the use of dinutuximab in both up-front and salvage therapy for high-risk NB, and the potential mechanisms of resistance to dinutuximab.
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PMID:Spotlight on dinutuximab in the treatment of high-risk neuroblastoma: development and place in therapy. 3061 34