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Related Experiment Video

Updated: Mar 20, 2026

Spontaneous Murine Model of Anaplastic Thyroid Cancer
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Therapeutically Targetable Mutational Landscape of Anaplastic Thyroid Cancer.

Murtaza Qazi1, Muhammad Danyal Ahsan2, Talar Telvizian1

  • 1Lankenau Medical Center, Wynnewood, PA.

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|March 18, 2026
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Summary

Anaplastic thyroid cancer (ATC) harbors actionable gene variants in 72% of cases, primarily in MAPK and PI3K pathways. These findings support targeted therapy trials for this aggressive cancer.

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Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • Anaplastic thyroid cancer (ATC) is a rare, aggressive malignancy with few effective treatments.
  • Current targeted therapies for ATC are limited to BRAF V600E mutations and NTRK fusions.
  • Identifying additional therapeutic targets is crucial for improving patient outcomes.

Purpose of the Study:

  • To characterize the landscape of somatic pathogenic gene variants (PGVs) in ATC.
  • To identify potentially actionable molecular targets beyond BRAF and NTRK.
  • To inform the development of targeted therapies for ATC.

Main Methods:

  • Somatic PGVs in 350 ATC tumors were analyzed using data from the American Association for Cancer Research Project GENIE database.
  • Genes were categorized into relevant pathways: MAPK, PI3K/Akt/mTOR, homologous recombination deficiency (HRD), and mismatch repair (MMR).
  • Next-generation sequencing and clinical data were utilized for variant identification and pathway analysis.

Main Results:

  • Pathogenic gene variants were detected in 57.7% of tumors within the MAPK pathway.
  • The PI3K/Akt/mTOR pathway showed PGVs in 26.6% of ATC samples.
  • Overall, 72.0% of ATC tumors harbored at least one PGV in the investigated potentially targetable pathways.

Conclusions:

  • A significant majority (72%) of anaplastic thyroid cancer cases possess somatic PGVs in actionable pathways.
  • These findings provide a strong rationale for biomarker-driven basket trials.
  • Investigating targeted therapies in ATC patients based on identified PGVs may improve treatment efficacy.