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Completed

NCT Number: NCT05752669

Oxidative Stress and Mitochondrial TERT in Papillary Thyroid Cancer.

Oxidative stress (OS) could be involved in the progression of papillary thyroid cancer (PTC). Indeed, thyroid differentiation genes are silenced by a mechanism controlled by NOX4-derived OS. On the other hand, TERT contributes to mitochondrial OS protection, which could increase the resistance of cancer cells to therapeutic agents. The investigators aim to address the role of OS and mitochondrial TERT in the progression and therapeutic resistance of PTC. OS and TERT subcellular localization will be investigated in 150 PTCs and correlated to the genetic and expression profile of the tumors and to the clinical and prognostic features of the patients. Mechanisms implicated in TERT mitochondrial migration and the contribution of mitochondrial TERT to tumor progression will be investigated in cancer cell lines and primary cell cultures. This study will allow to identify OS as a marker of therapeutic resistance in PTC and will open new opportunities for the development of novel treatments targeting ROS generation/TERT nuclear export.

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Key information

Conditions

Papillary Thyroid Cancer Adenocarcinoma Adenocarcinoma, Papillary Carcinoma Endocrine Gland Neoplasms Endocrine System Diseases Head and Neck Neoplasms Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial Thyroid Cancer, Papillary Thyroid Diseases Thyroid Neoplasms

Sex eligibility

All sexes

Study type

Observational

Primary location

Istituto Auxologico Italiano

Milan, Italy

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Patients with papillary thyroid cancer
  • Patients whose tumor and contralateral healthy tissues can be collected for the analyses

Exclusion criteria

  • patients who did not provide consent
  • patients lost at follow-up
  • tissues not adequate for the analyses

Treatment and study plan

Primary outcomes

  1. H202 generation (nmol/mg tissue) in papillary thyroid cancer and in corresponding normal tissues.

    Time frame: months 1-24

  2. TERT mitochondrial localization (TERT/VDAC) in papillary thyroid tumors.

    Time frame: months 13-30

    TERT mitochondrial localization will be investigated by Western blot of mitochondrial fractions and normalized to VDAC protein expression.

  3. Effect of exogenous oxidative stress (H2O2) and therapeutic agents (BRAF, MEK and Src kinase inhibitors) on TERT nuclear to mitochondrial translocation in thyroid cancer cell lines.

    Time frame: month 19-30

    TERT mitochondrial translocation will be measured by immunofluorescence.

  4. Mitochondrial oxidative stress generation in cells lines treated with Src kinase inhibitors.

    Time frame: months 25-36

    Mitochondrial oxidative stress will be measured by immunofluorescence.

  5. Proliferation in cells lines treated with Src kinase inhibitors.

    Time frame: months 25-36

    Proliferation will be measured by a colorimetric assay.

  6. Apoptosis in cells lines treated with Src kinase inhibitors.

    Time frame: months 25-36

    Apoptosis will be measured by a luminometric assay.

  7. Migration in cells lines treated with Src kinase inhibitors.

    Time frame: months 25-36

    Migration will be measured by wound healing assays.

Secondary outcomes

  1. Genetic characterization of tumor tissues.

    Time frame: months 1-24

    Point mutations and fusions will be investigated in DNA and RNA, respectively,

  2. Expression profile of tumor tissues.

    Time frame: months 1-24

    The expression level of 16 thyroid function genes will be investigated by a custom RNA sequencing panel.

Sponsors and collaborators

Lead sponsor

Istituto Auxologico Italiano

Other

Collaborators

  • University of Milan

Registry information

Official study title

The Role of Oxidative Stress and Mitochondrial TERT in the Progression and Therapeutic Resistance of Papillary Thyroid Cancer.

Acronym: TEMPEST

Important dates

Study start
2021
Primary completion
2025
Study completion
2025
First posted
Mar 3, 2023
Registry last updated
Aug 21, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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