Identification of ANC-3 as a Novel Therapeutic Candidate for Anaplastic Thyroid Cancer Through Drug Screening and

Dorjsuren Tsagaankhuu1,2, Hyunwoo Baek2,3, Jungyoon Choi3

  • 1Department of Otorhinolaryngology-Head and Neck Surgery, Korea University Ansan Hospital, Korea University College of Medicine, Ansan 15355, Republic of Korea.

Insights

Anaplastic thyroid carcinoma (ATC) drug discovery is advanced by a new zebrafish xenograft screening platform. This system identified ANC-3, a promising compound that inhibits ATC cell growth and multiple cancer pathways.

Area of Science:

  • Oncology
  • Pharmacology
  • Genomics

Background:

  • Anaplastic thyroid carcinoma (ATC) is an aggressive cancer with limited treatment options.
  • There is a critical need for effective preclinical drug discovery platforms for ATC.

Purpose of the Study:

  • To identify novel therapeutic candidates for ATC using high-throughput screening.
  • To validate the efficacy of identified compounds using a zebrafish xenograft model.
  • To elucidate the molecular mechanisms of action for promising drug candidates.

Main Methods:

  • High-throughput compound screening of human ATC cell lines.
  • In vitro assays: cytotoxicity, migration, invasion, and colony-formation assays.
  • In vivo validation using zebrafish xenograft models with live fluorescence imaging.
  • Bulk RNA sequencing and pathway enrichment analysis.

Main Results:

  • ANC-3 was identified as a potent anticancer agent against ATC.
  • ANC-3 significantly inhibited ATC cell viability, migration, invasion, and clonogenic survival.
  • ANC-3 suppressed tumor growth in zebrafish xenograft models.
  • Transcriptomic analysis revealed ANC-3 modulates MAPK, Ras, and NF-κB signaling pathways.

Conclusions:

  • Zebrafish xenograft screening is a rapid and scalable platform for ATC drug discovery.
  • ANC-3 is a promising multi-pathway inhibitor for further preclinical development in ATC.

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