Response of Retinoic Acid in Patients with Radioactive Iodine-Refractory Thyroid Cancer: A Meta-Analysis

Pak, Kyoungjune; Shin, Seunghyeon; Kim, Seong-Jang; Kim, In Joo; Chang, Sun Ju; Koo, Phillip J.; Kwak, Jennifer; Kim, Jae-Ho

doi:10.1159/000484206

Cited by 15 publications

(7 citation statements)

References 40 publications

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“…A recent meta-analysis on retinoids in RAIR-DTC reported a pooled effect of 27.6% for increased radioiodine uptake and 17% for tumor response by RECIST criteria (Pak et al 2018) In these phase 1 and 2 trials, the 131I diagnostic WBS showed restoration of faint radioiodine uptake after various time periods of treatment in two out of six evaluable patients for the phase 1 study and 2 out of 16 patients for the phase 2. In the phase 2 trial (Sherman et al 2013), the faint radioiodine uptake observed on the diagnostic WBS was confirmed on the therapeutic WBS but without longterm benefit from the treatment.…”

Section: Retinoic Acidmentioning

confidence: 97%

Redifferentiation of radioiodine-refractory thyroid cancers

Buffet

Wassermann

Hecht

et al. 2020

Endocrine-Related Cancer

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The management of radioiodine refractory thyroid cancers (RAIR TC) is challenging for the clinician. Tyrosine kinase inhibitors classically prescribed in this setting can fail due to primary or acquired resistance or the necessity of drug withdrawal because of serious or moderate but chronic and deleterious adverse effects. Thus, the concept of redifferentiation strategy, which involves treating patients with one or more drugs capable of restoring radioiodine sensitivity for RAIR TC, has emerged. The area of redifferentiation strategy leads to the creation of new definitions of RAIR TC including persistent non radioiodine-avid patients and ‘true’ RAIR TC patients. The latter group presents a restored or increased radioiodine uptake in metastatic lesions but with no radiological response on conventional imaging, that is, progression of a metastatic disease, thus proving that they are ‘truly’ resistant to the radiation delivered by radioiodine. Unlike these patients, metastatic TC patients with restored radioiodine uptake offer the hope of prolonged remission or even cure of the disease as for radioiodine-avid metastatic TC. Here, we review the different redifferentiation strategies based on the underlying molecular mechanism leading to the sodium iodide symporter (NIS) and radioiodine uptake reinduction, that is, by modulating signaling pathways, NIS transcription, NIS trafficking to the plasma membrane, NIS post-transcriptional regulation, by gene therapy and other potential strategies. We discuss clinical trials and promising preclinical data of potential future targets.

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Section: Retinoic Acidmentioning

confidence: 97%

Redifferentiation of radioiodine-refractory thyroid cancers

Buffet

Wassermann

Hecht

et al. 2020

Endocrine-Related Cancer

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“…RA is the bioactive metabolite of vitamin A and plays a critical role in cellular differentiation during mammalian development. RA indeed may increase the expression of NIS mRNA in human FTC cells (Schmutzler et al 2002, Lan et al 2017a; however a recent meta-analysis reported that only a minority of patients with RAI-refractory DTC responded to RA treatment (Pak et al 2018). This poor response might be explained by the fact that RA treatment induces growth inhibition through retinoic acid receptor beta in cells where it is expressed, rather than through an increase of NIS at the plasma membrane (Elisei et al 2005).…”

Section: :11mentioning

confidence: 99%

Molecular mechanisms of resistance to kinase inhibitors in thyroid cancers

Hofmann

Kunnimalaiyaan

Wang

et al. 2022

Endocrine-Related Cancer

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Protein kinases play critical roles in cell survival, proliferation and motility. Their dysregulation is therefore a common feature in the pathogenesis of a number of solid tumors, including thyroid cancers. Inhibiting activated protein kinases has revolutionized thyroid cancer therapy, offering a promising strategy in treating tumors refractory to radioactive iodine treatment or cytotoxic chemotherapies. However, despite satisfactory early responses, these drugs are not curative and most patients inevitably progress due to drug resistance. This review summarizes up-to-date knowledge on various mechanisms that thyroid cancer cells develop to bypass protein kinase inhibition and outlines strategies that are being explored to overcome drug resistance. Understanding how cancer cells respond to drugs and identifying novel molecular targets for therapy still represents a major challenge for the treatment of these patients.

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“…Unfortunately, despite the interesting scientific basis, no studies have shown a definitive usefulness of vitamin A in thyroid cancer. Furthermore, one of the most recent reviews on this topic showed that only a minority of patients with RAI-R differentiated thyroid cancer respond well to retinoid treatment ( 54 ).…”

Section: Vitamin a And Thyroid Cancermentioning

confidence: 99%

The relationship between thyroid disorders and vitamin A.: A narrative minireview

et al. 2022

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The terms “vitamin A” and “retinoids” encompass a group of fat-soluble compounds essential for human nutrition. Some of them (retinol, retinal, 9-cis-retinoic acid, tretinoin, and 13-cis-retinoic acid) are fully natural, while others are synthetic compounds used mostly for therapeutic purposes. Some evidence indicates that the nutritional status of these retinoids (i.e., the presence or absence of deficiency) is able to modulate thyroid gland metabolism. Vitamin A deficiency is tightly correlated with structural and functional impairment of the thyroid gland and is often associated with iodine deficiency. Furthermore, retinoids are involved in different immune functions, as well as in the process of activation, proliferation, and differentiation of regulatory T cells (Treg). This is particularly significant given the high prevalence of thyroid autoimmune disorders, whose pathogenesis seems to be related to the altered homeostasis of regulatory T cells. Retinoids are also involved in the modulation of gene expression via their interaction with nuclear receptors, and they also act as cofactors in cell growth and differentiation. The ability of retinoic acid to increase iodine uptake and sodium-iodine symporter activity in human thyroid cancer cell lines suggests that some retinoids and their derivatives may be of use in the treatment of different thyroid tumors. This minireview summarizes the current knowledge on the link between nutritional intake of vitamin A and various thyroid disorders.

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Response of Retinoic Acid in Patients with Radioactive Iodine-Refractory Thyroid Cancer: A Meta-Analysis

Cited by 15 publications

References 40 publications

Redifferentiation of radioiodine-refractory thyroid cancers

Redifferentiation of radioiodine-refractory thyroid cancers

Molecular mechanisms of resistance to kinase inhibitors in thyroid cancers

The relationship between thyroid disorders and vitamin A.: A narrative minireview

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