Children's Oncology Group's 2013 blueprint for research: Neuroblastoma

Park, Julie R.; Bagatell, Rochelle; London, Wendy B.; Maris, John M.; Cohn, Susan L.; Mattay, Katherine M.; Hogarty, Michael D.

doi:10.1002/pbc.24433

Cited by 320 publications

(316 citation statements)

References 120 publications

(182 reference statements)

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“…Despite aggressive treatment with chemotherapy, surgery, radiation, high-dose chemotherapy with autologous stem cell rescue, anti-GD2 immunotherapy, and retinoic acid, about 50% of children with high-risk neuroblastoma experience disease relapse. Children with relapsed/refractory neuroblastoma have a <10% chance of survival (1). In addition, an increasing number of neuroblastoma survivors develop multisystem deficiencies (2) and secondary malignancies (3) as a result of the toxic chemotherapy exposures.…”

Section: Introductionmentioning

confidence: 99%

Identification of Cancer-Targeted Tropomyosin Inhibitors and Their Synergy with Microtubule Drugs

Currier

Stehn

Swain

et al. 2017

Molecular Cancer Therapeutics

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Actin filaments, with their associated tropomyosin polymers, and microtubules are dynamic cytoskeletal systems regulating numerous cell functions. While antimicrotubule drugs are wellestablished, antiactin drugs have been more elusive. We previously targeted actin in cancer cells by inhibiting the function of a tropomyosin isoform enriched in cancer cells, Tpm3.1, using a first-in-class compound, TR100. Here, we screened over 200 other antitropomyosin analogues for anticancer and ontarget activity using a series of in vitro cell-based and biochemical assays. ATM-3507 was selected as the new lead based on its ability to disable Tpm3.1-containing filaments, its cytotoxicity potency, and more favorable drug-like characteristics. We tested ATM-3507 and TR100 alone and in combination with antimicrotubule agents against neuroblastoma models in vitro and in vivo. Both ATM-3507 and TR100 showed a high degree of synergy in vitro with vinca alkaloid and taxane antimicrotubule agents. In vivo, combination-treated animals bearing human neuroblastoma xenografts treated with antitropomyosin combined with vincristine showed minimal weight loss, a significant and profound regression of tumor growth and improved survival compared with control and either drug alone. Antitropomyosin combined with vincristine resulted in G 2 -M phase arrest, disruption of mitotic spindle formation, and cellular apoptosis. Our data suggest that small molecules targeting the actin cytoskeleton via tropomyosin sensitize cancer cells to antimicrotubule agents and are tolerated together in vivo. This combination warrants further study.

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Section: Introductionmentioning

confidence: 99%

Identification of Cancer-Targeted Tropomyosin Inhibitors and Their Synergy with Microtubule Drugs

Currier

Stehn

Swain

et al. 2017

Molecular Cancer Therapeutics

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“…Neuroblastoma is the most common heterogeneous extracranial neoplastic disease of childhood, developing from immature nerve cells found in several areas of the body or where groups of nerve cells exist (1). The metastatic phenotype of neuroblastoma is associated to activation of several genes, some of which are deeply involved in angiogenesis (2,3).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA miR-93-5p regulates expression of IL-8 and VEGF in neuroblastoma SK-N-AS cells

et al. 2016

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Abstract. The role of the microRNA miR-93-5p on the secretome profile and the expression levels of vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) was investigated in the neuroblastoma SK-N-AS cell line by Bio-Plex analysis and RT-qPCR. The results indicate that VEGF and IL-8 are the major miR-93-5p molecular targets. This conclusion was based on in vitro transfection with pre-miR-93-5p and anti-miR-93-5p; these treatments inversely modulated both VEGF and IL-8 gene expression and protein release in the neuroblastoma SK-N-AS cell line. Computational analysis showed the presence of miR-93-5p consensus sequences in the 3'UTR region of both VEGF and IL-8 mRNAs, predicting possible interaction with miR-93-5p and confirming a potential regulatory role of this microRNA.

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“…SIOPN is now evaluating this 10-day mAb regimen, with and without a modified IL2 subcutaneous regimen. Ongoing studies by COG are evaluating the potential for using the ch14.18 mAb in the same courses as chemotherapy, rather than after completion of chemotherapy [70] (clinicaltrials.gov NCT01767194).…”

Section: Gd2-car T Cells I High-risk Nbl (19) Cr In 3 Ptsmentioning

confidence: 99%

Anti-GD2 MABS and Next-Generation mAb-Based Agents for Cancer Therapy

2016

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Tumor-specific monoclonal antibodies (mAbs) have demonstrated efficacy in the clinic, becoming an important approach for cancer immunotherapy. Due to its limited expression on normal tissue, the GD2 disialogangloside expressed on neuroblastoma cells is an excellent candidate for mAb therapy. In 2015, dinutuximab (an anti-GD2 mAb) was approved by the US FDA and is currently used in a combination immunotherapeutic regimen for the treatment of children with high-risk neuroblastoma. Here, we review the extensive preclinical and clinical development of anti-GD2 mAbs and the different mechanisms by which they mediate tumor cell killing. In addition, we discuss different mAb-based strategies that capitalize on the targeting ability of anti-GD2 mAbs to potentially deliver, as monotherapy, or in combination with other treatments, improved antitumor efficacy.

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Children's Oncology Group's 2013 blueprint for research: Neuroblastoma

Cited by 320 publications

References 120 publications

Identification of Cancer-Targeted Tropomyosin Inhibitors and Their Synergy with Microtubule Drugs

Identification of Cancer-Targeted Tropomyosin Inhibitors and Their Synergy with Microtubule Drugs

MicroRNA miR-93-5p regulates expression of IL-8 and VEGF in neuroblastoma SK-N-AS cells

Anti-GD2 MABS and Next-Generation mAb-Based Agents for Cancer Therapy

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