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

Author(s):Show less -

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

Affiliation

^[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

• Document type: Review article
• Source: CANCERS; v. 13, n. 3 FEB 2021.
• Web of Science Citations: 0

Abstract

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)

• FAPESP's process: 14/50943-1 - INCT 2014: on Oncogenomics and Therapeutic Inovations
• Grantee: Dirce Maria Carraro
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 18/06269-5 - Combining genomic approaches to determine the genetics causes of rare cancers in children, adolescents and young adults
• Grantee: Giovana Tardin Torrezan
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/25541-8 - Molecular characterization of soft-tissue sarcomas: integration of translational preclinical models and functional study of genetic alterations with clinical relevance
• Grantee: Tiago Góss dos Santos
• Support Opportunities: Regular Research Grants