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Updated: Jul 10, 2025

Spontaneous Murine Model of Anaplastic Thyroid Cancer
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Discovery of New Anti-Cancer Agents against Patient-Derived Sorafenib-Resistant Papillary Thyroid Cancer

Yuna Kim1, Hyeok Jun Yun2, Kyung Hwa Choi3

  • 1Department of Internal Medicine, Institute of Gastroenterology, Gangnam Severance Hospital, Yonsei University College of Medicine, 211 Eonjuro, Gangnam-gu, Seoul 06273, Republic of Korea.

International Journal of Molecular Sciences
|November 25, 2023
PubMed

Insights

Researchers identified novel drug targets for thyroid cancer by focusing on the sarco/endoplasmic reticulum calcium ATPase (SERCA). New SERCA inhibitors showed significant tumor shrinkage in resistant cancer models, offering hope for improved treatments.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • Thyroid cancer, while often treatable, can develop resistance to therapies like sorafenib.
  • Drug-resistant metastasis and recurrence are major causes of treatment failure and mortality in thyroid cancer patients.
  • Identifying novel therapeutic targets is crucial for overcoming anti-cancer drug resistance.

Purpose of the Study:

  • To identify and validate novel drug targets for anti-cancer drug-resistant papillary thyroid cancer (PTC).
  • To investigate the role of sarco/endoplasmic reticulum calcium ATPase (SERCA) in sorafenib-resistant PTC.
  • To discover novel SERCA inhibitors for potential therapeutic application.

Main Methods:

  • Comparative analysis of patient-derived sorafenib-resistant and sorafenib-sensitive PTC cells.
  • Focus on targeting the sarco/endoplasmic reticulum calcium ATPase (SERCA) pathway.
  • Virtual screening to identify novel SERCA inhibitors (candidates 33 and 36).
  • In vivo validation using a xenograft tumor model of sorafenib-resistant PTC.

Main Results:

  • Novel SERCA inhibitors (candidates 33 and 36) were identified through virtual screening.
  • These novel inhibitors demonstrated significant tumor shrinkage in a xenograft model.
  • The findings highlight SERCA as a promising target in drug-resistant PTC.

Conclusions:

  • The identified SERCA inhibitors hold clinical value for treating drug-resistant thyroid cancer.
  • These findings support the development of novel combinatorial strategies against highly malignant cancer cells.
  • Targeting SERCA offers a promising avenue for overcoming sorafenib resistance in papillary thyroid cancer.
Keywords:
anti-cancer drug resistant papillary thyroid cancerpatient-derived papillary thyroid cancersorafenib

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