Related Experiment Video

Updated: Dec 29, 2025

Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells
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Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells

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Targeting DUBs to degrade oncogenic proteins

Anjali Cremer1,2, Kimberly Stegmaier3

  • 1Department of Pediatric Oncology, Dana-Farber Cancer Institute and Boston Children's Hospital, Harvard Medical School, Boston, MA, 02215, USA.

British Journal of Cancer
|February 5, 2020
PubMed

Insights

Targeted protein degradation is a novel cancer therapy. HBX19818, a USP10 inhibitor, degrades spleen tyrosine kinase (SYK) and FLT3, killing acute myeloid leukemia (AML) cells.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Targeted protein degradation is a promising strategy in oncology.
  • Deubiquitinase (DUB) inhibitors represent a novel therapeutic avenue.
  • Acute myeloid leukemia (AML) remains a challenging malignancy.

Discussion:

  • The deubiquitinase USP10 is a potential therapeutic target in AML.
  • Inhibition of USP10 leads to the degradation of key oncogenic proteins.
  • Dual degradation of SYK and FLT3 has significant implications for AML treatment.

Key Insights:

  • HBX19818, a novel USP10 inhibitor, induces targeted protein degradation.
  • The compound effectively degrades both spleen tyrosine kinase (SYK) and FLT3.
  • This dual degradation results in the death of AML cells, highlighting a new therapeutic mechanism.

Outlook:

  • USP10 inhibitors like HBX19818 show potential for AML therapy.
  • Further research may explore combination therapies involving DUB inhibitors.
  • This approach could be extended to other hematological malignancies or solid tumors.

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