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Updated: Oct 27, 2025

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies
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Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies

Published on: September 30, 2016

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Degradation of CCNK/CDK12 is a druggable vulnerability of colorectal cancer

Sebastian M Dieter1, Christine Siegl2, Paula L Codó3

  • 1Department of Translational Medical Oncology, National Center for Tumor Diseases (NCT) Dresden and German Cancer Research Center (DKFZ), 01307 Dresden, Germany; Translational Functional Cancer Genomics, NCT and DKFZ Heidelberg, 69120 Heidelberg, Germany.

Cell Reports
|July 21, 2021
PubMed

Insights

A new drug, NCT02, targets cyclin K (CCNK) and CDK12 degradation in a subset of metastatic colorectal cancer (CRC) patients, offering a novel therapeutic strategy for this difficult-to-treat cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • Metastatic colorectal cancer (CRC) requires novel treatments to improve patient outcomes.
  • Existing therapies face challenges with resistance and toxicity.

Purpose of the Study:

  • To identify novel small molecules for CRC treatment.
  • To investigate the mechanism of action and efficacy of identified compounds.

Main Methods:

  • Screening of small molecules against patient-derived CRC spheroids.
  • Mechanistic studies involving ubiquitination, proteasomal degradation, and gene knockout.
  • In vitro and in vivo efficacy assessments in CRC models.

Main Results:

  • NCT02 identified as a promising candidate with specific activity against a subset of CRC spheroids.
  • NCT02 induces ubiquitination and degradation of cyclin K (CCNK) and CDK12.
  • CCNK/CDK12 depletion inhibits CRC cell proliferation and tumor growth.
  • Sensitivity to NCT02 correlates with TP53 deficiency and consensus molecular subtype 4.

Conclusions:

  • Targeted CCNK/CDK12 degradation is an effective strategy for a subset of metastatic CRC.
  • Drug-induced proteolysis shows potential for treating difficult-to-treat cancers.
  • NCT02 represents a promising therapeutic avenue for specific CRC patient populations.
Keywords:
CCNKCDK12colorectal cancermolecular glue degradertargeted protein degradation

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