Small-Cell Carcinoma of the Ovary, Hypercalcemic Type-Genetics, New Treatment Targets, and Current Management Guidelines.

No Thumbnail Available
Change log
Tischkowitz, Marc 
Banerjee, Susana 
Hendricks, William PD  ORCID logo

Small-cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare and highly aggressive ovarian malignancy. In almost all cases, it is associated with somatic and often germline pathogenic variants in SMARCA4, which encodes for the SMARCA4 protein (BRG1), a subunit of the SWI/SNF chromatin remodeling complex. Approximately 20% of human cancers possess pathogenic variants in at least one SWI/SNF subunit. Because of their role in regulating many important cellular processes including transcriptional control, DNA repair, differentiation, cell division, and DNA replication, SWI/SNF complexes with mutant subunits are thought to contribute to cancer initiation and progression. Fewer than 500 cases of SCCOHT have been reported in the literature and approximately 60% are associated with hypercalcemia. SCCOHT primarily affects females under 40 years of age who usually present with symptoms related to a pelvic mass. SCCOHT is an aggressive cancer, with long-term survival rates of 30% in early-stage cases. Although various treatment approaches have been proposed, there is no consensus on surveillance and therapeutic strategy. An international group of multidisciplinary clinicians and researchers recently formed the International SCCOHT Consortium to evaluate current knowledge and propose consensus surveillance and therapeutic recommendations, with the aim of improving outcomes. Here, we present an overview of the genetics of this cancer, provide updates on new treatment targets, and propose management guidelines for this challenging cancer.

Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Small Cell, Chemotherapy, Adjuvant, Chromatin Assembly and Disassembly, DNA Helicases, Female, Gynecology, Humans, Hypercalcemia, Medical Oncology, Mutation, Nuclear Proteins, Ovarian Neoplasms, Ovariectomy, Ovary, Practice Guidelines as Topic, Radiotherapy, Adjuvant, Stem Cell Transplantation, Survival Rate, Transcription Factors, Treatment Outcome
Journal Title
Clin Cancer Res
Conference Name
Journal ISSN
Volume Title
American Association for Cancer Research (AACR)
All rights reserved
European Research Council (310018)
Eve Appeal research charity