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There are several types of targeted therapies against...
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Related Experiment Video

Updated: Oct 6, 2025

Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down
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Transcriptome-Guided Drug Repurposing for Aggressive SCCs.

Roland Zauner1, Monika Wimmer1, Sonja Dorfer1

  • 1EB House Austria, Research Program for Molecular Therapy of Genodermatoses, Department of Dermatology and Allergology, University Hospital of the Paracelsus Medical University Salzburg, 5020 Salzburg, Austria.

International Journal of Molecular Sciences
|January 21, 2022
PubMed
Summary
This summary is machine-generated.

This study identified potential new treatments for aggressive cutaneous squamous cell carcinoma (SCC) in organ transplant recipients and RDEB patients. Repurposed drugs targeting MEK signaling show promise for these rare, aggressive SCC types.

Keywords:
drug repurposingepidermolysis bullosaorgan transplant recipientssquamous cell carcinoma

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Area of Science:

  • Oncology
  • Genomics
  • Pharmacology

Background:

  • Cutaneous squamous cell carcinoma (SCC) incidence is rising, with aggressive forms linked to immunosuppression and recessive dystrophic epidermolysis bullosa (RDEB).
  • Despite different causes, these aggressive SCC subtypes share molecular similarities, offering a target for novel therapeutic strategies.

Purpose of the Study:

  • To identify drugs for repurposing to treat rare and aggressive cutaneous squamous cell carcinoma (SCC) subtypes.
  • To leverage transcriptomic similarities between SCCs in organ transplant recipients and RDEB patients, alongside head and neck SCC data, for drug discovery.

Main Methods:

  • Utilized an in silico approach based on reversing tumor-specific gene expression signatures towards healthy tissue profiles.
  • Analyzed differentially expressed genes to identify tumor signatures and mined drug-perturbation data from extensive compound libraries.
  • Focused on drugs targeting key molecules within specific signaling pathways, such as the MEK pathway.

Main Results:

  • Identified selumetinib as a drug candidate targeting the MEK signaling cascade.
  • The identified drugs demonstrate potential for reversing malignant phenotypes in aggressive SCCs.
  • The study successfully pinpointed therapeutic candidates by analyzing transcriptomic data and drug interactions.

Conclusions:

  • Selumetinib and other MEK pathway inhibitors are promising candidates for treating aggressive SCCs in immunocompromised and RDEB patients.
  • Transcriptome-based drug repurposing is an effective strategy for identifying treatments for rare and aggressive cancers.
  • This research provides a foundation for developing targeted therapies for specific, high-risk SCC populations.