Use of anlotinib in intra-abdominal desmoplastic small round cell tumors: a case report and literature review

Chen, Huimin; Feng, Ge

doi:10.2147/ott.s190333

Cited by 19 publications

(32 citation statements)

References 19 publications

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“…Second-line treatment for patients with recurrent disease that have been used are vascular endothelial growth factor (receptor) (VEGF(R))-, mammalian target of rapamycin (mTOR)-, and platelet-derived growth factor receptor (PDGFR)-based targeted therapy. These treatments can again induce favorable, however short-lived, responses (Chen and Feng 2019;Italiano et al 2013;Menegaz et al 2018;Tarek et al 2018;Thijs et al 2010). Overall, treatment results in a 5-year overall survival (OS) rate of 15-25%, which shows the high unmet need for novel treatments in DSRCTs (Bent et al 2016;Subbiah et al 2018).…”

Section: Introductionmentioning

confidence: 99%

Olaparib and temozolomide in desmoplastic small round cell tumors: a promising combination in vitro and in vivo

Erp¹,

Houdt²,

Hillebrandt-Roeffen³

et al. 2020

J Cancer Res Clin Oncol

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Purpose Desmoplastic small round cell tumors (DSRCTs) are highly malignant and very rare soft tissue sarcomas with a high unmet need for new therapeutic options. Therefore, we examined poly(ADP-ribose) polymerase 1 (PARP1) and Schlafen-11 (SLFN11) expression in DSRCT tumor tissue and the combination of PARP inhibitor olaparib with the alkylating agent temozolomide (TMZ) in a preclinical DSRCT model. Methods PARP1 and SLFN11 have been described as predictive biomarkers for response to PARP inhibition. Expression of PARP1 and SLFN11 was assessed in 16 and 12 DSRCT tumor tissue samples, respectively. Effects of single-agent olaparib, and olaparib and TMZ combination treatment were examined using the preclinical JN-DSRCT-1 model. In vitro, single-agent and combination treatment effects on cell viability, the cell cycle, DNA damage and apoptosis were examined. Olaparib and TMZ combination treatment was also assessed in vivo. Results PARP1 and SLFN11 expression was observed in 100% and 92% of DSRCT tumor tissues, respectively. Olaparib treatment reduced cell viability and cell migration in a dose-dependent manner in vitro. Drug synergy between olaparib and TMZ was observed in vitro and in vivo. Combination treatment led to a cell-cycle arrest and induction of DNA damage and apoptosis, even when combined at low dosages. Conclusion We show high PARP1 and SLFN11 expression in DSRCT tumor material and antitumor effects following olaparib and TMZ combination treatment in a preclinical DSRCT model. This suggests that olaparib and TMZ combination treatment could be a potential treatment option for DSRCTs.Keywords Desmoplastic small round cell tumor (DSRCT) · Poly(ADP-ribose) polymerase (PARP) · Schlafen-11 (SLFN11) · Olaparib · Temozolomide · Combination treatment Abbreviations DSRCT Desmoplastic small round cell tumor ES Ewing sarcoma PARP Poly(ADP-ribose) polymerase SLFN11 Schlafen-11 SSB Single-stranded breaks STS Soft tissue sarcoma TMZ Temozolomide Electronic supplementary material The online version of this article (https ://doi.org/10.1007/s0043 2-020-03211 -z) contains supplementary material, which is available to authorized users.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Section: Introductionmentioning

confidence: 99%

Olaparib and temozolomide in desmoplastic small round cell tumors: a promising combination in vitro and in vivo

Erp¹,

Houdt²,

Hillebrandt-Roeffen³

et al. 2020

J Cancer Res Clin Oncol

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“…O uso de outros agentes também foi relatado. O erlotinibe, um inibidor multialvo da tirosina quinase, levou à resposta parcial em um relato de caso 19 . A atividade contra a doença foi relatada com uso de pazopanibe 20,21 e eribulin 22 .…”

Section: Discussionunclassified

Tumor Desmoplásico de Pequenas Células Redondas: Relato de Caso

Costa

Reis

Loureiro

et al. 2018

Rev. Brasileira.De.Cancerologia

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Introdução: O tumor desmoplásico de pequenas células redondas é uma rara neoplasia que se inicia e se espalha pela superfície peritoneal. Foi descrito pela primeira vez em 1989 e, em 1991, houve seu reconhecimento como entidade clínica e patológica distintas. Relato do caso: Homem de 34 anos apresentou quadro de dor abdominal e perda de peso, evoluindo para obstrução intestinal dois meses após. A laparotomia demonstrou grande massa abdominopélvica irressecável. O laudo anatomopatológico associado à imuno-histoquímica evidenciou diagnóstico de tumor desmoplásico de pequenas células redondas. A tomografia computadorizada confirmou derrame pleural bilateral, implantes peritoneais e massas abdominais e pélvicas. Realizou-se quimioterapia com carbo/taxol com intervalo de 21 dias. Substituiu-se o esquema para VAC/IE com intervalo de 21 dias, com resposta parcial, porém ainda se mantendo um tumor irressecável. Houve piora progressiva da performance do paciente, com evolução ao óbito por obstrução intestinal no 15º mês de seguimento. Conclusão: O tumor desmoplásico de pequenas células redondas, em razão da sua raridade, continua sendo um desafio para o diagnóstico e o tratamento.

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“…In the largest DSRCT comprehensive genomic profile study, no secondary mutation on c-MET was found [ 103 ]. There is a case report of a patient with intra-abdominal DSRCT who received anlotinib, a multi-kinase inhibitor that targets c-Met, for the progressive disease after surgery and first-line chemotherapy showing stable disease for 4 months [ 116 ].…”

Section: Treatmentmentioning

confidence: 99%

Desmoplastic Small Round Cell Tumor: A Review of Main Molecular Abnormalities and Emerging Therapy

Mello

Campos

Santos

et al. 2021

Cancers

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Desmoplastic small round cell tumor (DSRCT) is an extremely rare, aggressive sarcoma affecting adolescents and young adults with male predominance. Generally, it originates from the serosal surface of the abdominal cavity. The hallmark characteristic of DSRCT is the EWSR1–WT1 gene fusion. This translocation up-regulates the expression of PDGFRα, VEGF and other proteins related to tumor and vascular cell proliferation. Current management of DSRCT includes a combination of chemotherapy, radiation and aggressive cytoreductive surgery plus intra-peritoneal hyperthermic chemotherapy (HIPEC). Despite advances in multimodal therapy, outcomes remain poor since the majority of patients present disease recurrence and die within three years. The dismal survival makes DSRCT an orphan disease with an urgent need for new drugs. The treatment of advanced and recurrent disease with tyrosine kinase inhibitors, such as pazopanib, sunitinib, and mTOR inhibitors was evaluated by small trials. Recent studies using comprehensive molecular profiling of DSRCT identified potential therapeutic targets. In this review, we aim to describe the current studies conducted to better understand DSRCT biology and to explore the new therapeutic strategies under investigation in preclinical models and in early phase clinical trials.

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Use of anlotinib in intra-abdominal desmoplastic small round cell tumors: a case report and literature review

Cited by 19 publications

References 19 publications

Olaparib and temozolomide in desmoplastic small round cell tumors: a promising combination in vitro and in vivo

Olaparib and temozolomide in desmoplastic small round cell tumors: a promising combination in vitro and in vivo

Tumor Desmoplásico de Pequenas Células Redondas: Relato de Caso

Desmoplastic Small Round Cell Tumor: A Review of Main Molecular Abnormalities and Emerging Therapy

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