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Publication-only abstracts (abstract number preceded by an "e"), published in conjunction with the 2019 ASCO Annual Meeting but not presented at the Meeting, can be found online only.

Effective targeted antitumor activity of the antimicrobial agent taurolidine against relapsed/refractory neuroblastoma: Cytotoxicity, target modulation and tumor xenograft studies.

Sub-category:
Pediatric Solid Tumors

Category:
Pediatric Oncology

Meeting:
2019 ASCO Annual Meeting

Abstract No:
e21502

Citation:
J Clin Oncol 37, 2019 (suppl; abstr e21502)

Author(s): Lucy Swift, Chunfen Zhang, Antony Pfaffle, Paul Chew, Olga Kovalchuk, Tanya Maria Trippett, Aru Narendran; Alberta Children's Hospital, Calgary, AB, Canada; Cormedix, Berkeley Heights, NJ; University of Lethbridge, Lethbridge, AB, Canada; Memorial Sloan Kettering Cancer Center, New York, NY; University of Calgary, Calgary, AB, Canada

Abstract Disclosures

Abstract:

Background: Neuroblastoma (NB) is the most common extracranial solid tumor and one of the most complex and difficult to treat diseases in pediatrics. Currently, even with highly aggressive treatment protocols, the prognosis for patients with high-risk and relapsed NB remains poor. Hence, there is a clear need to identify new agents and novel therapeutic strategies for the treatment of these children. Taurolidine (TRD) is derived from the aminosulfoacid taurine and has known anti-microbial and anti-inflammatory properties. TRD has demonstrated anti-neoplastic activity against a range of aggressive human tumors. We present mechanistic evidence and supportive preclinical data from in vitro and animal models of refractory NB for the development of an early phase clinical trial incorporating TRD. Methods: For in vitro activity studies, a panel of cell lines derived from patients with relapsed NB (n = 6) and normal control cells were treated with increasing concentrations of TRD and cell viability was measured by alamar blue assay. Phase-contrast light microscopy, western blotting, time-lapse video microscopy and analysis of global gene expression by RNA-Seq were used to evaluate target modulation and induction of cell death pathways. Bioluminescence imaging of mice bearing NB xenografts treated with TRD was used to investigate the efficacy of TRD in vivo. Results: Cell survival data showed that TRD is cytotoxic against NB cell lines in vitro (mean IC50 value 100 µM, range 65-135 µM). Phase-contrast and time-lapse video microscopy confirmed the antitumor effects of TRD. Western blot analyses identified that TRD induced target modulation and an effective apoptotic cascade, resulting in PARP cleavage. Gene expression analyses and signaling pathway activation scores indicated alterations in the Notch, MAPK and IL-10 signaling pathways. Xenograft studies further validated the in vivo activity of TRD with decreased tumor burden in treated mice and a measurable improvement in survival. Conclusions: Our study provides key pre-clinical data on the activity and mechanism of action of TRD against NB. The findings support the rationale for further evaluation of TRD for the treatment of relapsed/refractory NB patients in an early phase clinical trial.

 
Other Abstracts in this Sub-Category:

 

1. Randomized phase 2 trial of the combination of vincristine and irinotecan with or without temozolomide, in children and adults with refractory or relapsed rhabdomyosarcoma (RMS).

Meeting: 2019 ASCO Annual Meeting Abstract No: 10000 First Author: Anne Sophie Defachelles
Category: Pediatric Oncology - Pediatric Solid Tumors

 

2. Temozolomide versus irinotecan-temozolomide for children with relapsed and refractory high risk neuroblastoma (RR-HRNB): Results of the BEACON-Neuroblastoma randomized phase 2 trial—A European Innovative Therapies for Children with Cancer (ITCC) - International Society of Pediatric Oncology Europe Neuroblastoma Group (SIOPEN) trial.

Meeting: 2019 ASCO Annual Meeting Abstract No: 10001 First Author: Lucas Moreno
Category: Pediatric Oncology - Pediatric Solid Tumors

 

3. Phase 1/1B trial to assess the activity of entrectinib in children and adolescents with recurrent or refractory solid tumors including central nervous system (CNS) tumors.

Meeting: 2019 ASCO Annual Meeting Abstract No: 10009 First Author: Giles W. Robinson
Category: Pediatric Oncology - Pediatric Solid Tumors

 

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