Evaluation of Romidepsin for Clinical Activity and Radioactive Iodine Reuptake in Radioactive Iodine–Refractory Thyroid Carcinoma

Sherman, Eric J.; Su, Yungpo Bernard; Lyall, Ashima; Schöder, Heiko; Fury, Matthew G.; Ghossein, Ronald; Haque, Sofia; Lisa, Donna; Shaha, Ashok R.; Tuttle, R. Michael; Pfister, David G.

doi:10.1089/thy.2012.0393

Cited by 61 publications

(36 citation statements)

References 20 publications

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“…This study had poor accrual after a grade 5 adverse event. 89 Another drug, Axitinib (a selective inhibitor of vascular endothelial growth factor receptors VEGFR 1, 2, and 3), was studied in 60 patients with advanced thyroid cancers in a multi-institutional phase 2 trial; partial responses were seen in 18 patients (30% objective response rate), and 38% patients showed stable disease at > or = 16 weeks. 90 …”

Section: Discoveries In Thyroid Cancer Biology Provide a Rationale Fomentioning

confidence: 99%

Novel Approaches to Thyroid Cancer Treatment and Response Assessment

Grewal

Schöder

2016

Seminars in Nuclear Medicine

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The incidence of thyroid cancer has been on the rise. After total thyroidectomy of well differentiated thyroid tumors with intermediate or high-risk features on pathology, radioiodine remains one of the mainstays as the standard therapy for thyroid remnant ablation as well as treatment of metastatic disease. SPECT/CT, a relatively newer modality, has shown to play a pivotal role predominantly in the post-therapy setting by changing the risk stratification of patients with thyroid cancer. In the case of radioiodine failure, other modalities such as FDG PET/CT have been shown to provide prognostic information in terms of metabolic activity and external beam radiation therapy, thereby playing a role in disease management. The role of newer redifferentiation drugs has been evaluated with the use of I-124 PET/CT.

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Section: Discoveries In Thyroid Cancer Biology Provide a Rationale Fomentioning

confidence: 99%

Novel Approaches to Thyroid Cancer Treatment and Response Assessment

Grewal

Schöder

2016

Seminars in Nuclear Medicine

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“…Romidepsin is currently being used in more than 50 interventional trials, alone or in combination regimens (see clinicaltrials.gov). Romidepsin is often coupled with canonical chemotherapies (NCT00379639), demethylating agents (NCT01537744), and proteasome inhibitors (PIs; NCT00765102) (91,194,202).…”

Section: Romidepsinmentioning

confidence: 99%

Targeting Histone Deacetylases in Diseases: Where Are We?

Benedetti

Conte

Altucci

2015

Antioxidants & Redox Signaling

102

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Significance: Epigenetic inactivation of pivotal genes involved in cell growth is a hallmark of human pathologies, in particular cancer. Histone acetylation balance obtained through opposing actions of histone deacetylases (HDACs) and histone acetyltransferases is one epigenetic mechanism controlling gene expression and is, thus, associated with disease etiology and progression. Interfering pharmacologically with HDAC activity can correct abnormalities in cell proliferation, migration, vascularization, and death. Recent Advances: Histone deacetylase inhibitors (HDACi) represent a new class of cytostatic agents that interfere with the function of HDACs and are able to increase gene expression by indirectly inducing histone acetylation. Several HDACi, alone or in combination with DNA-demethylating agents, chemopreventive, or classical chemotherapeutic drugs, are currently being used in clinical trials for solid and hematological malignancies, and are, thus, promising candidates for cancer therapy. Critical Issues: (i) Non-specific (off-target) HDACi effects due to activities unassociated with HDAC inhibition. (ii) Advantages/disadvantages of non-selective or isoformdirected HDACi. (iii) Limited number of response-predictive biomarkers. (iv) Toxicity leading to dysfunction of critical biological processes. Future Directions: Selective HDACi could achieve enhanced clinical utility by reducing or eliminating the serious side effects associated with current first-generation non-selective HDACi. Isoform-selective and pan-HDACi candidates might benefit from the identification of biomarkers, enabling better patient stratification and prediction of response to treatment. Antioxid. Redox Signal. 23, 99-126.Shaping the Epigenome E pigenetic mechanism(s) allow genetically identical cells to adopt different phenotypes regulating transcriptional availability of the genome through differential chromatin marking and packaging (137), creating a network of mutually reinforcing or counteracting signals (192). A key aspect of epigenetics is that chromatin marks can be preserved and/or changed according to environmental, developmental, or pathological needs. These very complex and plastic steps are achieved via the activity of initiators (such as long noncoding RNA), writers (which establish the epigenetic mark, such as histone acetyltransferases), readers (which interpret the epi-mark), and erasers (which remove the epi-mark, such as histone deacetylases, or HDACs) (41, 232). In concert, remodelers (which reposition nucleosomes) and insulators (which build boundaries between epi-domains) create, maintain, and modulate the three-dimensional structure of networking within a cell (223). It is now clear that genetic and epigenetic mechanisms influence each other, cooperating to enable the acquisition of hallmarks of human cancer (89). The frequency of epi-target mutations seen in cancers underlines the relevance of mutations in epigenetic modifiers in cancer (213) and corroborates the concept that deregulation of epigenetic cont...

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“…Many of them target signaling nodes known to participate in the development and progression of thyroid cancers, most of which have reduced NIS expression. Specifically, inhibitors for MEK [29–31], PI3K [32, 33], BRAF [31], HDAC [34–38], and TGF-β [39] are shown to increase thyroid NIS expression, and these reagents are in clinical trials for various diseases. Accordingly, the use of these reagents to further enhance TSH-stimulated thyroidal RAI uptake to facilitate I-131 therapy for thyroid cancer patients could be imminent, if their effects are validated in preclinical animal models and clinical trials.…”

Section: Modulation Of Nis-mediated Iodide Influx Iodide Efflux Andmentioning

confidence: 99%

Modulation of Sodium Iodide Symporter in Thyroid Cancer

et al. 2014

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Radioactive iodine (RAI) is a key therapeutic modality for thyroid cancer. Loss of RAI uptake in thyroid cancer inversely correlates with patient’s survival. In this review, we focus on the challenges encountered in delivering sufficient doses of I-131 to eradicate metastatic lesions without increasing the risk of unwanted side effects. Sodium iodide symporter (NIS) mediates iodide influx, and NIS expression and function can be selectively enhanced in thyroid cells by thyroid-stimulating hormone. We summarize our current knowledge of NIS modulation in normal and cancer thyroid cells, and we propose that several reagents evaluated in clinical trials for other diseases can be used to restore or further increase RAI accumulation in thyroid cancer. Once validated in preclinical mouse models and clinical trials, these reagents, mostly small-molecule inhibitors, can be readily translated into clinical practice. We review available genetically engineered mouse models of thyroid cancer in terms of their tumor development and progression as well as their thyroid function. These mice will not only provide important insights into the mechanisms underlying the loss of RAI uptake in thyroid tumors but will also serve as preclinical animal models to evaluate the efficacy of candidate reagents to selectively increase RAI uptake in thyroid cancers. Taken together, we anticipate that the optimal use of RAI in the clinical management of thyroid cancer is yet to come in the near future.

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Evaluation of Romidepsin for Clinical Activity and Radioactive Iodine Reuptake in Radioactive Iodine–Refractory Thyroid Carcinoma

Abstract: We observed preliminary signs of in vivo reversal of RAI resistance after treatment with romidepsin. However, no major responses were observed and accrual was poor after the grade 5 AE.

Cited by 61 publications

References 20 publications

Novel Approaches to Thyroid Cancer Treatment and Response Assessment

Novel Approaches to Thyroid Cancer Treatment and Response Assessment

Targeting Histone Deacetylases in Diseases: Where Are We?

Modulation of Sodium Iodide Symporter in Thyroid Cancer

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