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

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Mello, Celso Abdon ^[1] ; Batista Campos, Fernando Augusto ^[1] ; Santos, Tiago Goss ^{[2, 3]} ; Gobo Silva, Maria Leticia ^[4] ; Torrezan, Giovana Tardin ^{[3, 5]} ; Costa, Felipe D'Almeida ^[6] ; Formiga, Maria Nirvana ^[1] ; Nicolau, Ulisses ^[1] ; Nascimento, Antonio Geraldo ^[6] ; Silva, Cassia ^[1] ; Curado, Maria Paula ^[7] ; Nakagawa, Suely Akiko ^[8] ; Lopes, Ademar ^[8] ; Aguiar Jr, Samuel

Afiliação do(s) autor(es)

^[1] AC Camargo Canc Ctr, Dept Med Oncol, BR-01509010 Sao Paulo - Brazil

^[2] AC Camargo Canc Ctr, Int Ctr Res CIPE, Lab Tumor Biol & Biomarkers, BR-01509010 Sao Paulo - Brazil

^[3] Natl Inst Sci & Technol Oncogen & Therapeut Innov, BR-05403010 Sao Paulo - Brazil

^[4] AC Camargo Canc Ctr, Dept Radiat Oncol, BR-01509010 Sao Paulo - Brazil

^[5] AC Camargo Canc Ctr, Int Ctr Res CIPE, Genom & Mol Biol Grp, BR-01508010 Sao Paulo - Brazil

^[6] AC Camargo Canc Ctr, Dept Pathol, BR-01509010 Sao Paulo - Brazil

^[7] AC Camargo Canc Ctr, Dept Epidemiol, BR-01508010 Sao Paulo - Brazil

^[8] AC Camargo Canc Ctr, Dept Surg, BR-01509010 Sao Paulo - Brazil

• Tipo de documento: Artigo de Revisão
• Fonte: CANCERS; v. 13, n. 3 FEB 2021.
• Citações Web of Science: 0

Resumo

Simple Summary Desmoplastic small round cell tumor is a rare neoplasm with extremely aggressive behavior. Despite the multimodal treatment for newly diagnosed patients with chemotherapy, cytoreductive surgery and radiation, the cure rate is still low. For relapsed or progressive disease, there is limited data regarding second and third-line therapies. Novel agents have shown only modest activity. Recent molecular changes have been identified in this disease and this opens opportunities to be explored in future clinical trials. 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 PDGFR alpha, 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. (AU)

• Processo FAPESP: 14/50943-1 - INCT 2014: de Oncogenômica e Inovação Terapêutica
• Beneficiário: Dirce Maria Carraro
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 18/06269-5 - Utilização de abordagens genômicas combinadas para investigar as causas genéticas de tumores raros em crianças, adolescentes e adultos jovens
• Beneficiário: Giovana Tardin Torrezan
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 18/25541-8 - Caracterização molecular de sarcomas de partes moles: integração de modelos pré-clínicos translacionais e estudo funcional de alterações genéticas com relevância clínica
• Beneficiário: Tiago Góss dos Santos
• Modalidade de apoio: Auxílio à Pesquisa - Regular