Nature Communications (Feb 2019)
CDK4/6 inhibitors target SMARCA4-determined cyclin D1 deficiency in hypercalcemic small cell carcinoma of the ovary
- Yibo Xue,
- Brian Meehan,
- Elizabeth Macdonald,
- Sriram Venneti,
- Xue Qing D. Wang,
- Leora Witkowski,
- Petar Jelinic,
- Tim Kong,
- Daniel Martinez,
- Geneviève Morin,
- Michelle Firlit,
- Atefeh Abedini,
- Radia M. Johnson,
- Regina Cencic,
- Jay Patibandla,
- Hongbo Chen,
- Andreas I. Papadakis,
- Aurelie Auguste,
- Iris de Rink,
- Ron M. Kerkhoven,
- Nicholas Bertos,
- Walter H. Gotlieb,
- Blaise A. Clarke,
- Alexandra Leary,
- Michael Witcher,
- Marie-Christine Guiot,
- Jerry Pelletier,
- Josée Dostie,
- Morag Park,
- Alexander R. Judkins,
- Ralf Hass,
- Douglas A. Levine,
- Janusz Rak,
- Barbara Vanderhyden,
- William D. Foulkes,
- Sidong Huang
Affiliations
- Yibo Xue
- Department of Biochemistry, McGill University
- Brian Meehan
- Department of Pediatrics, McGill University
- Elizabeth Macdonald
- Centre for Cancer Therapeutics, Ottawa Hospital Research Institute
- Sriram Venneti
- Pathology and Neuropathology, University of Michigan Medical School
- Xue Qing D. Wang
- Department of Biochemistry, McGill University
- Leora Witkowski
- Department of Human Genetics, McGill University
- Petar Jelinic
- Gynecologic Oncology, Laura and Isaac Perlmutter Cancer Center, NYU Langone Medical Center
- Tim Kong
- Department of Biochemistry, McGill University
- Daniel Martinez
- Children’s Hospital of Philadelphia Research Institute
- Geneviève Morin
- Department of Biochemistry, McGill University
- Michelle Firlit
- Gynecologic Oncology, Laura and Isaac Perlmutter Cancer Center, NYU Langone Medical Center
- Atefeh Abedini
- Centre for Cancer Therapeutics, Ottawa Hospital Research Institute
- Radia M. Johnson
- Department of Biochemistry, McGill University
- Regina Cencic
- Department of Biochemistry, McGill University
- Jay Patibandla
- Gynecologic Oncology, Laura and Isaac Perlmutter Cancer Center, NYU Langone Medical Center
- Hongbo Chen
- School of Pharmaceutical Sciences (Shenzhen), Sun Yat-Sat University
- Andreas I. Papadakis
- Department of Biochemistry, McGill University
- Aurelie Auguste
- Department of Cancer Medicine, Gustave Roussy, INSERM U981
- Iris de Rink
- Genomics Core Facility, The Netherlands Cancer Institute
- Ron M. Kerkhoven
- Genomics Core Facility, The Netherlands Cancer Institute
- Nicholas Bertos
- Department of Biochemistry, McGill University
- Walter H. Gotlieb
- Division of Gynecologic Oncology, Segal Cancer Center, Jewish General Hospital, McGill University
- Blaise A. Clarke
- Department of Laboratory Medicine and Pathobiology, University of Toronto, University Health Network
- Alexandra Leary
- Department of Cancer Medicine, Gustave Roussy, INSERM U981
- Michael Witcher
- Department of Oncology, McGill University
- Marie-Christine Guiot
- Department of Pathology, Montreal Neurological Hospital/Institute, McGill University Health Centre
- Jerry Pelletier
- Department of Biochemistry, McGill University
- Josée Dostie
- Department of Biochemistry, McGill University
- Morag Park
- Department of Biochemistry, McGill University
- Alexander R. Judkins
- Department of Pathology and Laboratory Medicine, Children’s Hospital Los Angeles, Keck School of Medicine of University of Southern California
- Ralf Hass
- Biochemistry and Tumor Biology Laboratory, Department of Gynecology and Obstetrics, Medical University Hannover
- Douglas A. Levine
- Gynecologic Oncology, Laura and Isaac Perlmutter Cancer Center, NYU Langone Medical Center
- Janusz Rak
- Department of Pediatrics, McGill University
- Barbara Vanderhyden
- Centre for Cancer Therapeutics, Ottawa Hospital Research Institute
- William D. Foulkes
- Department of Human Genetics, McGill University
- Sidong Huang
- Department of Biochemistry, McGill University
- DOI
- https://doi.org/10.1038/s41467-018-06958-9
- Journal volume & issue
-
Vol. 10,
no. 1
pp. 1 – 15
Abstract
Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is driven by SMARCA4 loss. Here the authors demonstrate that SCCOHT cells are highly sensitive to CDK4/6 inhibition and provide mechanistic insights, whereby this druggable vulnerability is driven by cyclin D1 deficiency induced by SMARCA4 loss.
