Cancer and Metastasis Reviews

, Volume 38, Issue 3, pp 525–535 | Cite as

Current management of succinate dehydrogenase–deficient gastrointestinal stromal tumors

  • Pushpa Neppala
  • Sudeep Banerjee
  • Paul T. Fanta
  • Mayra Yerba
  • Kevin A. Porras
  • Adam M. BurgoyneEmail author
  • Jason K. SicklickEmail author


Gastrointestinal stromal tumors (GISTs) are increasingly recognized as having diverse biology. With the development of tyrosine kinase inhibitors molecularly matched to oncogenic KIT and PDGFRA mutations, GISTs have become a quintessential model for precision oncology. However, about 5–10% of GIST lack these driver mutations and are deficient in succinate dehydrogenase (SDH), an enzyme that converts succinate to fumarate. SDH deficiency leads to accumulation of succinate, an oncometabolite that promotes tumorigenesis. SDH-deficient GISTs are clinically unique in that they generally affect younger patients and are associated with GIST-paraganglioma hereditary syndrome, also known as Carney-Stratakis Syndrome. SDH-deficient GISTs are generally resistant to tyrosine-kinase inhibitors, the standard treatment for advanced or metastatic GIST. Thus, surgical resection is the mainstay of treatment for localized disease, but recurrence is common. Clinical trials are currently underway investigating systemic agents for treatment of advanced SDH-deficient GIST. However, further studies are warranted to improve our understanding of SDH-deficient GIST disease biology, natural history, surgical approaches, and novel therapeutics.


Gastrointestinal stromal tumors GIST Succinate dehydrogenase Tyrosine kinase inhibitors SDH 



Pushpa Neppala: Study design, data analysis, article drafting, and critical review of the manuscript.

Sudeep Banerjee: Data analysis, article drafting, and critical review of the manuscript.

Paul T. Fanta: Critical review of the manuscript.

Mayra Yerba: Data analysis, article drafting, and critical review of the manuscript.

Kevin A. Porras: Article drafting.

Adam M. Burgoyne: Data analysis, article drafting, and critical review of the manuscript.

Jason K. Sicklick: Study design, data analysis, article drafting, and critical review of the manuscript.

All authors had approved the final article.

Funding information

This work was supported by the Society for Surgery of the Alimentary Tract (SSAT) Mentored Research Award (S.B), UC San Diego GIST Research Fund (J.K.S.), NIH K08CA168999 (J.K.S.), NIH R21CA192072 (J.K.S.), and NIH R01CA226803 (J.K.S.).

Compliance with ethical standards

Conflict of interest

Jason Sicklick receives research funds from Foundation Medicine, Amgen Pharmaceuticals, and Novartis Pharmaceuticals, as well as consultant fees from Deciphera Pharmaceuticals, Loxo, and Grand Rounds. Adam Burgoyne receives consultant fees from Exelixis and Eisai. All other authors have no relationships to disclose.

Informed consent

Not applicable.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Pushpa Neppala
    • 1
  • Sudeep Banerjee
    • 2
    • 3
  • Paul T. Fanta
    • 4
    • 5
  • Mayra Yerba
    • 2
  • Kevin A. Porras
    • 1
  • Adam M. Burgoyne
    • 5
    Email author
  • Jason K. Sicklick
    • 2
    • 4
    Email author
  1. 1.UC San Diego School of MedicineUniversity of California, San DiegoLa JollaUSA
  2. 2.Division of Surgical Oncology, Department of Surgery, UC San Diego Moores Cancer CenterUniversity of California, San DiegoLa JollaUSA
  3. 3.Department of SurgeryDavid Geffen School of Medicine at UCLALos AngelesUSA
  4. 4.Center for Personalized Cancer Therapy, UC San Diego Moores Cancer CenterUniversity of California, San DiegoLa JollaUSA
  5. 5.Division of Hematology-Oncology, Department of Medicine, UC San Diego Moores Cancer CenterUniversity of California, San DiegoLa JollaUSA

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