CIC-DUX4 sarcomas

Curr Opin Oncol. 2022 Jul 1;34(4):342-347. doi: 10.1097/CCO.0000000000000855. Epub 2022 Jun 22.

Abstract

Purpose of review: CIC-DUX4 sarcoma (CDS) is a high-grade undifferentiated round cells sarcoma that belongs to the undifferentiated round cell sarcomas family. It represents less than one percent of sarcomas, defining a rarest among rare malignancies. It affects young adults, displaying soft tissue mass. Considered very aggressive, a high proportion of cases display an advanced disease with lung metastasis at diagnosis. Here we discuss recent progress in molecular characterization of CDS, the main tracks of CDS biology and the current and future prospects of therapeutic approaches.

Recent findings: CDS is characterized by a specific oncogenic translocation CIC::DUX4 that induce ETV4 overexpression. Patients with CDS show an aggressive clinical course and have a significantly unfavorable outcome compared to Ewing sarcoma. As of today, there is a lack of consensus on whether they should be treated with an Ewing-like approach, as currently done by most sites, or regarded as high-grade soft tissue sarcoma (STS). Anyway, when feasible, combination regimens including anthracycline and alkylating agents should be favored and patients should not benefit from a therapeutic de-escalation. Overall, registration within clinical trials and prospective registries is recommended.

Summary: Overall, CDS showed a poor prognosis regardless of the patterns of treatment that warrant biological studies to better understand the disease.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor
  • Humans
  • Oncogene Proteins, Fusion
  • Prospective Studies
  • Sarcoma* / drug therapy
  • Sarcoma* / genetics
  • Sarcoma, Ewing*
  • Sarcoma, Small Cell* / pathology
  • Soft Tissue Neoplasms*
  • Young Adult

Substances

  • Biomarkers, Tumor
  • CIC-DUX4 fusion protein, human
  • Oncogene Proteins, Fusion