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Molecular Cancer Therapeutics
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Companion Diagnostic, Pharmacogenomic, and Cancer Biomarkers

Anti-KIT DNA Aptamer for Targeted Labeling of Gastrointestinal Stromal Tumor

Sudeep Banerjee, Hyunho Yoon, Mayra Yebra, Chih-Min Tang, Mara Gilardi, Jayanth S. Shankara Narayanan, Rebekah R. White, Jason K. Sicklick and Partha Ray
Sudeep Banerjee
1Division of Surgical Oncology, Department of Surgery, Moores Cancer Center, University of California, San Diego, La Jolla, California.
2Department of Surgery, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California.
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Hyunho Yoon
1Division of Surgical Oncology, Department of Surgery, Moores Cancer Center, University of California, San Diego, La Jolla, California.
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Mayra Yebra
1Division of Surgical Oncology, Department of Surgery, Moores Cancer Center, University of California, San Diego, La Jolla, California.
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Chih-Min Tang
1Division of Surgical Oncology, Department of Surgery, Moores Cancer Center, University of California, San Diego, La Jolla, California.
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Mara Gilardi
3Moores Cancer Center, University of California San Diego, La Jolla, California.
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Jayanth S. Shankara Narayanan
1Division of Surgical Oncology, Department of Surgery, Moores Cancer Center, University of California, San Diego, La Jolla, California.
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Rebekah R. White
1Division of Surgical Oncology, Department of Surgery, Moores Cancer Center, University of California, San Diego, La Jolla, California.
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Jason K. Sicklick
1Division of Surgical Oncology, Department of Surgery, Moores Cancer Center, University of California, San Diego, La Jolla, California.
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  • For correspondence: pray@health.ucsd.edu jsicklick@ucsd.edu
Partha Ray
1Division of Surgical Oncology, Department of Surgery, Moores Cancer Center, University of California, San Diego, La Jolla, California.
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  • ORCID record for Partha Ray
  • For correspondence: pray@health.ucsd.edu jsicklick@ucsd.edu
DOI: 10.1158/1535-7163.MCT-19-0959 Published May 2020
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Abstract

Gastrointestinal stromal tumor (GIST), the most common sarcoma, is characterized by KIT protein overexpression, and tumors are frequently driven by oncogenic KIT mutations. Targeted inhibition of KIT revolutionized GIST therapy and ushered in the era of precision medicine for the treatment of solid malignancies. Here, we present the first use of a KIT-specific DNA aptamer for targeted labeling of GIST. We found that an anti-KIT DNA aptamer bound cells in a KIT-dependent manner and was highly specific for GIST cell labeling in vitro. Functionally, the KIT aptamer bound extracellular KIT in a manner similar to KIT mAb staining, and was trafficked intracellularly in vitro. The KIT aptamer bound dissociated primary human GIST cells in a mutation agnostic manner such that tumors with KIT and PDGFRA mutations were labeled. In addition, the KIT aptamer specifically labeled intact human GIST tissue ex vivo, as well as peritoneal xenografts in mice with high sensitivity. These results represent the first use of an aptamer-based method for targeted detection of GIST in vitro and in vivo.

Footnotes

  • Note: Supplementary data for this article are available at Molecular Cancer Therapeutics Online (http://mct.aacrjournals.org/).

  • Mol Cancer Ther 2020;19:1173–82

  • Received October 7, 2019.
  • Revision received January 30, 2020.
  • Accepted February 28, 2020.
  • Published first March 3, 2020.
  • ©2020 American Association for Cancer Research.
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Molecular Cancer Therapeutics: 19 (5)
May 2020
Volume 19, Issue 5
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Anti-KIT DNA Aptamer for Targeted Labeling of Gastrointestinal Stromal Tumor
Sudeep Banerjee, Hyunho Yoon, Mayra Yebra, Chih-Min Tang, Mara Gilardi, Jayanth S. Shankara Narayanan, Rebekah R. White, Jason K. Sicklick and Partha Ray
Mol Cancer Ther May 1 2020 (19) (5) 1173-1182; DOI: 10.1158/1535-7163.MCT-19-0959

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Anti-KIT DNA Aptamer for Targeted Labeling of Gastrointestinal Stromal Tumor
Sudeep Banerjee, Hyunho Yoon, Mayra Yebra, Chih-Min Tang, Mara Gilardi, Jayanth S. Shankara Narayanan, Rebekah R. White, Jason K. Sicklick and Partha Ray
Mol Cancer Ther May 1 2020 (19) (5) 1173-1182; DOI: 10.1158/1535-7163.MCT-19-0959
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Molecular Cancer Therapeutics
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