Histone Deacetylase Inhibitors and Papillary Thyroid Cancer

Background/Aim: Papillary Thyroid Cancer (PTC) is the most common type of endocrine malignancy. Although PTC has an excellent prognosis, recurrent or metastatic disease could affect patients survival. Recent studies show that Histone Deacetylase Inhibitors (HDACIs) might be promising anticancer agents against PTC. The aim of this review is to evaluate the role of HDACIs as an additional modality in PTC treatment and to depict the latest trends of current research on this field. Materials and Methods: This literature review was performed using the MEDLINE database. The search strategy included terms: “thyroid cancer”, “papillary”, “HDAC”, “histone”, and “deacetylase”. Results: Agents, such as Suberoyl Anilide Hydroxamic Acid, Trichostatin A, Valproic Acid, Sodium butyrate, Panobinostat, Belinostat, Romidepsin, CUDC907 and N-Hydroxy-7-(2-naphthylthio)-Hepanomide have shown promising anti-cancer effects on PTC cell lines but fail to trigger major response in clinical trials. Conclusion: HDACIs have no significant effect as monotherapy against PTC but further research needs to be conducted in order to investigate their potential effect when used as an additional modality.

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Recent Progress in Histone Deacetylase Inhibitors as Anticancer Agents

Current Medicinal Chemistry ◽

10.2174/0929867325666181016163110 ◽

2020 ◽

Vol 27 (15) ◽

pp. 2449-2493 ◽

Cited By ~ 14

Author(s):

Loredana Cappellacci ◽

Diego R. Perinelli ◽

Filippo Maggi ◽

Mario Grifantini ◽

Riccardo Petrelli

Keyword(s):

Clinical Trials ◽

Histone Deacetylase ◽

Anticancer Agents ◽

Histone Deacetylase Inhibitors ◽

Cyclic Peptide ◽

Hdac Inhibitors ◽

Cancer Therapeutics ◽

Rational Drug Design ◽

Modeling Tools ◽

Anti Cancer

Histone Deacetylase (HDAC) inhibitors are a relatively new class of anti-cancer agents that play important roles in epigenetic or non-epigenetic regulation, inducing death, apoptosis, and cell cycle arrest in cancer cells. Recently, their use has been clinically validated in cancer patients resulting in the approval by the FDA of four HDAC inhibitors, vorinostat, romidepsin, belinostat and panobinostat, used for the treatment of cutaneous/peripheral T-cell lymphoma and multiple myeloma. Many more HDAC inhibitors are at different stages of clinical development for the treatment of hematological malignancies as well as solid tumors. Also, clinical trials of several HDAC inhibitors for use as anti-cancer drugs (alone or in combination with other anti-cancer therapeutics) are ongoing. In the intensifying efforts to discover new, hopefully, more therapeutically efficacious HDAC inhibitors, molecular modelingbased rational drug design has played an important role. In this review, we summarize four major structural classes of HDAC inhibitors (hydroxamic acid derivatives, aminobenzamide, cyclic peptide and short-chain fatty acids) that are in clinical trials and different computer modeling tools available for their structural modifications as a guide to discover additional HDAC inhibitors with greater therapeutic utility.

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Histone Deacetylase Inhibitor Depsipeptide Represses Nicotinamide N-Methyltransferase and Hepatocyte Nuclear Factor-1βGene Expression in Human Papillary Thyroid Cancer Cells

Thyroid ◽

10.1089/thy.2006.16.151 ◽

2006 ◽

Vol 16 (2) ◽

pp. 151-160 ◽

Cited By ~ 10

Author(s):

Jimin Xu ◽

Jerome M. Hershman

Keyword(s):

Thyroid Cancer ◽

Cancer Cells ◽

Histone Deacetylase ◽

Papillary Thyroid Cancer ◽

Histone Deacetylase Inhibitor ◽

Nuclear Factor ◽

Hepatocyte Nuclear Factor ◽

Papillary Thyroid ◽

Deacetylase Inhibitor ◽

Thyroid Cancer Cells

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Anti-cancer activity of myricetin against human papillary thyroid cancer cells involves mitochondrial dysfunction–mediated apoptosis

Biomedicine & Pharmacotherapy ◽

10.1016/j.biopha.2017.04.100 ◽

2017 ◽

Vol 91 ◽

pp. 378-384 ◽

Cited By ~ 24

Author(s):

Tae Kwun Ha ◽

Inae Jung ◽

Mi Eun Kim ◽

Sung Kwon Bae ◽

Jun Sik Lee

Keyword(s):

Thyroid Cancer ◽

Mitochondrial Dysfunction ◽

Cancer Cells ◽

Papillary Thyroid Cancer ◽

Papillary Thyroid ◽

Anti Cancer ◽

Thyroid Cancer Cells ◽

Cancer Activity

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MiR-129-5p is required for histone deacetylase inhibitor-induced cell death in thyroid cancer cells

Endocrine Related Cancer ◽

10.1530/erc-10-0257 ◽

2011 ◽

Vol 18 (6) ◽

pp. 711-719 ◽

Cited By ~ 56

Author(s):

Patrick Brest ◽

Sandra Lassalle ◽

Veronique Hofman ◽

Olivier Bordone ◽

Virginie Gavric Tanga ◽

...

Keyword(s):

Cell Death ◽

Thyroid Cancer ◽

Antitumor Activity ◽

Histone Deacetylase ◽

Histone Deacetylase Inhibitors ◽

Trichostatin A ◽

Primary Cultures ◽

Cancer Drugs ◽

Deacetylase Inhibitor ◽

Thyroid Cancer Cells

The molecular mechanism responsible for the antitumor activity of histone deacetylase inhibitors (HDACi) remains elusive. As HDACi have been described to alter miRNA expression, the aim of this study was to characterize HDACi-induced miRNAs and to determine their functional importance in the induction of cell death alone or in combination with other cancer drugs. Two HDACi, trichostatin A and vorinostat, induced miR-129-5p overexpression, histone acetylation and cell death in BCPAP, TPC-1, 8505C, and CAL62 cell lines and in primary cultures of papillary thyroid cancer (PTC) cells. In addition, miR-129-5p alone was sufficient to induce cell death and knockdown experiments showed that expression of this miRNA was required for HDACi-induced cell death. Moreover, miR-129-5p accentuated the anti-proliferative effects of other cancer drugs such as etoposide or human α-lactalbumin made lethal for tumor cells (HAMLET). Taken together, our data show that miR-129-5p is involved in the antitumor activity of HDACi and highlight a miRNA-driven cell death mechanism.

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Effects of Anti-Cancer Drug Sensitivity-Related Genetic Differences on Therapeutic Approaches in Refractory Papillary Thyroid Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms23020699 ◽

2022 ◽

Vol 23 (2) ◽

pp. 699

Author(s):

Hyeok Jun Yun ◽

Minki Kim ◽

Sang Yong Kim ◽

Sungsoon Fang ◽

Yonjung Kim ◽

...

Keyword(s):

Thyroid Cancer ◽

Combination Therapy ◽

Papillary Thyroid Cancer ◽

Thyroid Tissue ◽

Cancer Drug ◽

Papillary Thyroid ◽

Anti Cancer ◽

Well Differentiated

Thyroid cancer (TC) includes tumors of follicular cells; it ranges from well differentiated TC (WDTC) with generally favorable prognosis to clinically aggressive poorly differentiated TC (PDTC) and undifferentiated TC (UTC). Papillary thyroid cancer (PTC) is a WDTC and the most common type of thyroid cancer that comprises almost 70–80% of all TC. PTC can present as a solid, cystic, or uneven mass that originates from normal thyroid tissue. Prognosis of PTC is excellent, with an overall 10-year survival rate >90%. However, more than 30% of patients with PTC advance to recurrence or metastasis despite anti-cancer therapy; consequently, systemic therapy is limited, which necessitates expansion of improved clinical approaches. We strived to elucidate genetic distinctions due to patient-derived anti-cancer drug-sensitive or -resistant PTC, which can support in progress novel therapies. Patients with histologically proven PTC were evaluated. PTC cells were gained from drug-sensitive and -resistant patients and were compared using mRNA-Seq. We aimed to assess the in vitro and in vivo synergistic anti-cancer effects of a novel combination therapy in patient-derived refractory PTC. This combination therapy acts synergistically to promote tumor suppression compared with either agent alone. Therefore, genetically altered combination therapy might be a novel therapeutic approach for refractory PTC.

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