Response of preclinical medulloblastoma models to combination therapy with 13-cis retinoic acid and suberoylanilide hydroxamic acid (SAHA)

Spiller, Susan; Ditzler, Sally; Pullar, Barbara; Olson, James M.

doi:10.1007/s11060-007-9505-1

Cited by 64 publications

(33 citation statements)

References 25 publications

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“…79 Subsequently, in vivo studies have demonstrated that a combination of RA with the histone deacetylase inhibitor suberoylanilide hydroxamic acid is effective in medulloblastoma xenografts as well as in transgenic mice. 80 Currently, RA is tested in clinical studies for children with medulloblastoma ( Table 2). …”

Section: Future Directions For Medulloblastoma/spnetmentioning

confidence: 99%

Pediatric Brain Tumors: Current Treatment Strategies and Future Therapeutic Approaches

2009

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Summary:Pediatric CNS tumors are the most common solid tumors of childhood and the second most common cancer after hematological malignancies accounting for approximate 20 to 25% of all primary pediatric tumors. With over 3,000 new cases per year in the United States, childhood CNS tumors are the leading cause of death related to cancer in this population. The prognosis for these patients has improved over the last few decades, but current therapies continue to carry a high risk of significant side effects, especially for the very young. Currently a combination of surgery, radiation, and chemotherapy is often used in children greater than 3 years of age. This article will outline current and future therapeutic strategies for the most common pediatric CNS tumors, including primitive neuroectodermal tumors such as medulloblastoma, as well as astrocytomas and ependymomas.

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Section: Future Directions For Medulloblastoma/spnetmentioning

confidence: 99%

Pediatric Brain Tumors: Current Treatment Strategies and Future Therapeutic Approaches

2009

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“…Synergistic anti-tumour activity between histone deacetylase inhibitors and retinoids has been observed in a variety of preclinical models [24,25] . A study suggested that the HDAC inhibitor LAQ824 has a greater antitumor activity in combination with 13-cis-retinoic acid in melanoma tumors [24] .…”

Section: Combination Therapies Improve the Anticancer Activities Of Rmentioning

confidence: 99%

“…A study suggested that the HDAC inhibitor LAQ824 has a greater antitumor activity in combination with 13-cis-retinoic acid in melanoma tumors [24] . Another study showed that the intracranial tumors in ND2:SmoA1 mice treated with retinoid acid + SAHA + cisplatin showed a 4-fold increase in apoptosis over controls, and a 2-fold increase over animals receiving only SAHA or retinoid acid + SAHA [25] . We and others have shown that retinoids combined with histone deacetylase inhibitors are synergistic [26,27] .…”

Section: Combination Therapies Improve the Anticancer Activities Of Rmentioning

confidence: 99%

Combination therapies improve the anticancer activities of retinoids in neuroblastoma

Cheung¹

2015

WJCO

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Most therapeutic protocols for child cancers use cytotoxic agents which have a narrow therapeutic index, and resulting in severe acute and chronic toxicities to normal tissues. Despite the fact that most child cancer patients achieve complete remission after chemotherapy, death still occurs due to relapse of persistent minimal residual disease (MRD) which remaining after initial cytotoxic chemotherapy. Advanced neuroblastoma (NB) is a leading cause of cancer deaths in young children. Retinoids are an important component of advanced NB therapy at the stage of MRD, yet half of all patients treated with 13-cis -retinoic acid still relapse and die. More effective combination therapies, with a lower side-effect profile, are required to improve outcomes for NB. Fenretinide or N-4-hydroxyphenyl retinamide is a synthetic derivative of retinoic acid which works on cancer cells through nuclear receptor-dependent and -independent signalling mechanisms. Moreover, several histone deacetylase inhibitors have entered early phase trials, and, suberoylanilide hydroxamic acid has been approved for use in adult cutaneous T cell lymphoma. A number of studies suggest that retinoid signal activation is necessary for histone deacetylase inhibitor activity. A better understanding of their mechanism of actions will lead to more evidence-based retinoid combination therapies. Core tip: Neuroblastoma (NB) begins in embryonal neural crest cells, which later give rise to the sympathetic nervous system, and is caused in part by factors which arrest differentiation. In vitro , retinoids force susceptible cancer cells down a pathway of terminal differentiation and, have been part of the routine treatment of advanced NB for number of decades. Synergistic anti-tumour activity between histone deacetylase inhibitors and retinoids has been observed in a variety of preclinical models. This editorial note discusses some of these findings on the combination therapies for improving the anticancer activities of

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“…RA has been shown in preclinical models to cause apoptotic cell death in medulloblastoma by promoting BMP-2 transcription (Hallahan et al, 2003). This results in production of soluble BMP-2 protein that induces p38 MAP kinase phosphorylation and ultimately apoptosis (Spiller et al, 2008). Recently a phase 3 trial has been opened to treat medulloblastoma with RA.…”

Section: Targeted Treatmentmentioning

confidence: 99%

Chemotherapy of Medulloblastoma in Children

Schüler¹,

Hauser²,

Garami³

2011

Brain Tumors - Current and Emerging Therapeutic Strategies

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Response of preclinical medulloblastoma models to combination therapy with 13-cis retinoic acid and suberoylanilide hydroxamic acid (SAHA)

Abstract: RA + SAHA additively induce BMP-2 transcription and medulloblastoma apoptosis. The combination may act through a p38 MAPK independent mechanism. Efficacy increased with cisplatin, which has implications for clinical trial design.

Cited by 64 publications

References 25 publications

Pediatric Brain Tumors: Current Treatment Strategies and Future Therapeutic Approaches

Pediatric Brain Tumors: Current Treatment Strategies and Future Therapeutic Approaches

Combination therapies improve the anticancer activities of retinoids in neuroblastoma

Chemotherapy of Medulloblastoma in Children

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