Background: Tankyrase 1 (TNKS1) is a poly(ADP-ribose) polymerase involved in Wnt/β-catenin signaling, telomere maintenance, and genomic stability, making it an attractive therapeutic target in oncology. This study aimed to develop and apply an integrated computational workflow to identify novel TNKS1 inhibitor candidates. Methods: A curated dataset of experimentally validated TNKS1 inhibitors and property-matched DUD-E decoys was used to develop a consensus supervised machine learning (ML) model prioritization framework for ligand-based virtual screening, integrating Morgan fingerprints with three complementary classifiers. The model screened more than 700,000 compounds, and prioritized hits were evaluated by structure-based virtual screening (SBVS), Prime MM-GBSA binding free-energy refinement, and 500 ns molecular dynamics simulations (MDs). The top candidates were subsequently tested in an in vitro TNKS1 enzymatic inhibition assay. Results: The consensus ML framework prioritized 670 compounds, yielding five candidates for experimental testing. Compound 3 displayed the most favorable computational profile and was experimentally confirmed as a TNKS1 inhibitor candidate, exhibiting approximately 80% TNKS1 inhibition at 0.1 μM, whereas the remaining candidates showed only limited activity. Conclusions: The proposed workflow efficiently reduced a large chemical space to a focused set of TNKS1 inhibitor candidates while substantially reducing the experimental screening burden. Compound 3 represents a promising starting point for future structure–activity relationship studies and lead optimization in the context of TNKS1 inhibition. Moreover, this work highlights the value of integrating consensus ML, SBVS, and experimental validation to accelerate early-stage hit discovery for TNKS1 and other therapeutic targets.

The dynamic crosstalk between the tumor microenvironment (TME) and triple negative breast cancer (TNBC) cells plays a critical role in tumor progression and treatment resistance. Recent studies have highlighted the involvement of IL-20 receptor subunit alpha (IL-20RA) signaling in BC, where its overexpression modulates oncogenic pathways contributing to invasion and metastasis. Epigenetic dysregulation by Bromodomain and Extra-Terminal domain (BET) proteins critically influences key oncogenic pathways and cytokine expression in TNBC. Given that the BET-inhibitor JQ1 blocks TNBC cell growth, in this study we investigated its potential regulatory effects on the IL-20RA pathway. IL-20RA was found expressed across multiple BC cell lines compared to non-tumorigenic cells, with the highest levels detected in MDA-MB-231 and MDA-MB-468 cells. In both cell lines, JQ1 treatment significantly downregulated IL-20RA expression at gene and protein levels, accompanied by a reduction in the oncogenic JAK/STAT signaling pathway, and programmed death-ligand 1 (PD-L1) expression. Parallel in vivo experiments using TNBC xenograft models confirmed these findings, showing reduced IL-20RA and PD-L1 expression alongside decreased phosphorylation of JAK and STAT3. Overall, this study uncovers a novel interplay between BET inhibition and the IL-20RA/STAT3 axis, suggesting JQ1 as a valid therapeutic option for TNBC characterized by high IL-20RA expression.

The interleukin-20 (IL-20) cytokine subfamily, a subset of the IL-10 superfamily, includes IL-19, IL-20, IL-22, IL-24, and IL-26. Recently, their involvement in cancer biology has gained attention, particularly due to their impact on the tumor microenvironment (TME). Notably, IL-20 subfamily cytokines can exert both pro-tumorigenic and anti-tumorigenic effects, depending on the context. For example, IL-22 promotes tumor growth by enhancing cancer cell proliferation and protecting against apoptosis, whereas IL-24 demonstrates anti-tumor activity by inducing cancer cell death and inhibiting metastasis. Additionally, these cytokines influence macrophage polarization—an essential factor in the immune landscape of tumors—thereby modulating the inflammatory environment and immune evasion strategies. Understanding the dual role of IL-20 subfamily cytokines within the TME and their interactions with cancer cell hallmarks presents a promising avenue for therapeutic development. Interleukin-20 receptor antagonists are being researched for their role in cancer therapy, since they potentially inhibit tumor growth and progression. This review explores the relationship between IL-20 cytokines and key cancer-related processes, including growth and proliferative advantages, angiogenesis, invasion, metastasis, and TME support. Further research is necessary to unravel the specific mechanisms underlying their contributions to tumor progression and to determine their potential for targeted therapeutic strategies.

Cadmium (Cd), a carcinogenic component of tobacco, is a recognized risk factor for oral squamous cell carcinoma (OSCC). However, the molecular mechanisms underlying Cd-induced cytotoxicity in OSCC remain largely undefined. Here, we demonstrate that acute Cd exposure triggers ferroptosis in CAL27 OSCC cells derived from never-smokers, but not in SCC154 cells derived from smokers. Mechanistically, Cd outcompetes Fe, causing early iron depletion and activating the nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy. This process enhances the labile iron pool, promotes mitochondrial reactive oxygen species (ROS) generation, lipid peroxidation, and ferroptotic cell death. Notably, iron supplementation rescues CAL27 cells from Cd-induced damage, while exacerbating iron deficiency through transferrin receptor CD71 silencing amplifies cytotoxicity. Conversely, OSCC cells from smokers exhibit resistance to Cd toxicity, likely due to the overexpression of metallothionein 2A (MT2A), a heavy metal detoxification protein. Collectively, this study provides the evidence that ferritinophagy may act as a critical upstream driver of Cd-induced ferroptosis in OSCC cells derived from never-smokers, paving the way for potential ferroptosis-targeted therapeutic strategies in Cd-associated malignancies.

Rutin is a flavonoid glycoside found in many plants, known for its various pharmacological properties. However, its therapeutic potential is limited by its low water solubility, which restricts its bioavailability. Poloxamer 407 (P407) is a multifunctional excipient, which has proven effective in delivering poorly water-soluble drugs and promoting the healing process. Based on this information, this study investigates the wound healing potential of rutin-loaded P407 hydrogels, as an innovative pharmaceutical formulation. In vitro scratch assays on human keratinocytes revealed that combining rutin with P407 significantly enhances cell proliferation as compared to the single components. Moreover, the proposed hydrogel improved wound healing more effectively in rats than the free drug or the commercial wound dressing DuoDERM. Histological analyses confirmed that the formulation increased epithelialization and collagen synthesis in injured epidermises. These findings provide a strong rationale for the use of rutin-loaded P407 hydrogels for the treatment of skin injuries.

Targeting the tumor microenvironment (TME) is an attractive strategy for developing new drugs with anticancer activity against triple-negative breast cancer (TNBC). Interleukins (ILs) are key players in the TME cytokine network promoting cancer progression. Recent studies have highlighted the involvement of IL-20 receptor subunit alpha (IL-20RA) signalling in several cancers, including BC, in which IL-20RA is highly expressed, correlating with poor prognosis and influencing tumoral characteristics such as proliferation, cell death, invasiveness, and TME activity. Therefore, elucidating the role of the IL-20RA signalling pathway could form the basis for developing new therapeutic strategies. This study aimed to identify selective bioactive ligands able to affect IL-20RA activity. Virtual screening of over 310,000 compounds from both the DrugBank and ZINC15 databases identified four potential hit compounds tested for their anticancer activity against TNBC in vitro cell lines. Notably, Ritonavir, a well-known Human Immunodeficiency Virus Type 1 (HIV-1) protease inhibitor, significantly inhibited cell proliferation (about 40% at 50 µM, p < 0.001). IL-20 preincubation counteracted Ritonavir’s cytostatic effect while IL-20RA knockdown restored proliferation in Ritonavir-treated TNBC cells. In conclusion, these findings demonstrated that Ritonavir reduced TNBC cell proliferation through IL-20RA activity modulation, suggesting its potential repurposing as a therapeutic agent for TNBC management.

Tumor cells release exosomes, extracellular vesicle containing various bioactive molecules such as protein, DNA and RNA. The analysis of RNA molecules packaged in exosomes may provide new potential diagnostic or prognostic tumor biomarkers. The treatment of radioiodine-refractory aggressive thyroid cancer is still an unresolved clinical challenge, and the search for biomarkers that are detectable in early phase of the disease has become a fundamental goal for thyroid cancer research. By using transcriptome analysis, this study aimed to analyze the gene expression profiles of exosomes secreted by a non-tumorigenic thyroid cell line (Nthy-ori 3.1-exo) and a papillary thyroid cancer (TPC-1-exo) cell line, comparing them with those of cell bodies (Nthy-ori 3.1-cells and TPC-1-cells). A total of 9107 transcripts were identified as differentially expressed when comparing TPC-1-exo with TPC-1-cells and 5861 when comparing Nthy-ori 3.1-exo with Nthy-ori 3.1-cells. Among them, Sialic acid-binding immunoglobulin-like lectins 10 and 11 (SIGLEC10, SIGLEC11) and Keratin-associated protein 5 (KRTAP5-3) transcripts, genes known to be involved in cancer progression, turned out to be up-regulated only in TPC-1-exo. Gene ontology analysis revealed significantly enriched pathways, and only in TPC-1-exo were the differential expressed genes associated with an up-regulation in epigenetic processes. These findings provide a proof of concept that some mRNA species are specifically packaged in tumor-cell-derived exosomes and may constitute a starting point for the identification of new biomarkers for thyroid tumors.

Wound healing is a challenging clinical problem and efficient wound management is essential to prevent infection. This is best done by utilizing biocompatible materials in order to complete the healing in a rapid manner, with functional and esthetic outcomes. In this context, the zein protein fulfills the criteria of the ideal wound dressing which include non-toxicity and non-inflammatory stimulation. Zein gels containing rutin were prepared without any chemical refinement or addition of gelling agents in order to obtain a natural formulation characterized by antioxidant and anti-inflammatory properties to be proposed for the treatment of burns and sores. In vitro scratch assay showed that the proposed gel formulations promoted cell migration and a rapid gap closure within 24 h (similar to 90 %). In addition, the in vivo activities of rutin-loaded zein gel showed a greater therapeutic efficacy in Wistar rats, with a decrease of the wound area of about 90 % at day 10 with respect to the free form of the bioactive and to DuoDERM (R). The evaluation of various markers (TNF-alpha, IL-1 beta, IL-6, IL-10) confirmed the anti-inflammatory effect of the proposed formulation. The results illustrate the feasibility of exploiting the peculiar features of rutin-loaded zein gels for wound-healing purposes.

Introduction: Detachment from the extracellular matrix (ECM) is the first step of the metastatic cascade. It is a regulated process involving interaction between tumor cells and tumor microenvironment (TME). Iron is a key micronutrient within the TME. Here, we explored the role of iron in the ability of ovarian cancer cells to successfully detach from the ECM.Methods: HEY and PEO1 ovarian cancer cells were grown in 3D conditions. To mimic an iron rich TME, culture media were supplemented with 100 μM Fe3+. Cell mortality was evaluated by cytofluorimetric assay. The invasive potential of tumor spheroids was performed in Matrigel and documented with images and time-lapses. Iron metabolism was assessed by analyzing the expression of CD71 and FtH1, and by quantifying the intracellular labile iron pool (LIP) through Calcein-AM cytofluorimetric assay. Ferroptosis was assessed by quantifying mitochondrial reactive oxygen species (ROS) and lipid peroxidation through MitoSOX and BODIPY-C11 cytofluorimetric assays, respectively. Ferroptosis markers GPX4 and VDAC2 were measured by Western blot. FtH1 knockdown was performed by using siRNA.Results: To generate spheroids, HEY and PEO1 cells prevent LIP accumulation by upregulating FtH1. 3D HEY moderately increases FtH1, and LIP is only slightly reduced. 3D PEO1upregulate FtH1 and LIP results significantly diminished. HEY tumor spheroids prevent iron import downregulating CD71, while PEO1 cells strongly enhance it. Intracellular ROS drop down during the 2D to 3D transition in both cell lines, but more significantly in PEO1 cells. Upon iron supplementation, PEO1 cells continue to enhance CD71 and FtH1 without accumulating the LIP and ROS and do not undergo ferroptosis. HEY, instead, accumulate LIP, undergo ferroptosis and attenuate their sphere-forming ability and invasiveness. FtH1 knockdown significantly reduces the generation of PEO1 tumor spheroids, although without sensitizing them to ferroptosis.Discussion: Iron metabolism reprogramming is a key event in the tumor spheroid generation of ovarian cancer cells. An iron-rich environment impairs the sphere-forming ability and causes cell death only in ferroptosis sensitive cells. A better understanding of ferroptosis sensitivity could be useful to develop effective treatments to kill ECM-detached ovarian cancer cells.

The cellular prion protein (PrP C ) is well-known for its involvement, under its pathogenic protease-resistant form (PrP Sc ), in a group of neurodegenerative diseases, known as prion diseases. PrP C is expressed in nervous system, as well as in other peripheral organs, and has been found overexpressed in several types of solid tumors. Notwithstanding, studies in recent years have disclosed an emerging role for PrP C in various cancer associated processes. PrP C has high binding affinity for 37/67 kDa laminin receptor (RPSA), a molecule that acts as a key player in tumorigenesis, affecting cell growth, adhesion, migration, invasion and cell death processes. Recently, we have characterized at cellular level, small molecules able to antagonize the direct PrP C binding to RPSA and their intracellular trafficking. These findings are very crucial considering that the main function of RPSA is to modulate key events in the metastasis cascade. Elucidation of the role played by PrP C /RPSA interaction in regulating tumor development, progression and response to treatment, represents a very promising challenge to gain pathogenetic information and discover novel specific biomarkers and/or therapeutic targets to be exploited in clinical settings. This review attempts to convey a detailed description of the complexity surrounding these multifaceted proteins from the perspective of cancer hallmarks, but with a specific focus on the role of their interaction in the control of proliferation, migration and invasion, genome instability and mutation, as well as resistance to cell death controlled by autophagic pathway.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

The release of molecules in exosomal cargoes is involved in tumor development and progression. We compared the profiles of exosomal microRNAs released by two thyroid cancer cell lines (TPC-1 and K1) with that of non-tumorigenic thyroid cells (Nthy-ori-3-1), and we explored the network of miRNA–target interaction. After extraction and characterization of exosomes, expression levels of microRNAs were investigated using custom TaqMan Advanced array cards, and compared with those expressed in the total cell extracts. The functional enrichment and network-based analysis of the miRNAs’ targets was also performed. Five microRNAs (miR-21-5p, miR-31-5p, miR-221-3p, miR-222-3p, and let-7i-3p) were significantly deregulated in the exosomes of tumor cells vs. non-tumorigenic cells, and three of them (miR-31-5p, miR-222-3p, and let-7i-3p) in the more aggressive K1 compared to TPC-1 cells. The network analysis of the five miRNAs identified some genes as targets of more than one miRNAs. These findings permitted the identification of exosomal microRNAs secreted by aggressive PTC cells, and indicated that their main targets are regulators of the tumor microenvironment. A deeper analysis of the functional role of the targets of exosomal miRNAs will provide further information on novel targets of molecular treatments for these neoplasms.

Oxidative stress is the result of an imbalance between pro-oxidant and antioxidant species at cellular level, also defined as a lack in redox signaling and control. Despite small amounts of reactive oxygen or nitrogen species (ROS and RNS) are essential to maintain cell homeostasis and redox signaling, currently, it is well understood that chronic oxidative stress conditions are responsible for several key biomolecule modifications, such as, DNA impairment, lipid peroxidation and protein carbonylation (Pisoschi et al., 2021). Ultimately, oxidative stress is tightly implicated in the pathophysiology of chronic disorders, such as diabetes, neurodegenerative and cardiovascular diseases, and cancer (Sharifi-Rad et al., 2020). Antioxidants are the first line of defense against the injurious effects of pro-oxidant species. By definition, an antioxidant is a molecule that prevents or retards the oxidation of a biomolecule both acting as radical scavengers (primary antioxidants) or modulating cellular mechanisms responsible for reactive species production (secondary antioxidants). They can be classified as enzymatic or nonenzymatic, or according to their mechanism of action, as preventive antioxidants, radical scavengers, repair antioxidants or antioxidants exploiting an adaptation mechanism. Finally, they can also be classified on the basis of their origin as endogenous, such as enzymes or small molecules produced by metabolic routes, and exogenous such as synthetic molecules and plant-derived secondary metabolites, normally not synthesized by human body whose intake is mainly due to diet or dietary supplements (Pisoschi et al., 2021). Literature describing the chemistry, absorption, and metabolism, mechanism of action and biological involvements of such antioxidants is very extensive, dating back to 1960 (Yeung et al., 2019). Nevertheless, the research on protective agents against oxidative stress never stopped growing, still resulting in a hot topic for the recent literature. The articles presented in this Research Topic further gathered scientific data and provided experimental evidence, therefore contributing to the potential development of new solutions for antioxidant implementation, development, and integration in therapeutic strategies. Recent discoveries assessing that oxidative stress is the main risk factor for several diseases without therapy, such as neurodegenerative diseases (NDs i.e., Alzheimer disease) and autoimmune disorders (i.e., multiple sclerosis, lupus, rheumatoid arthritis), opened new potential therapeutic approaches for their modulation. In addition, recent studies disclosing the involvement of oxidative stress in mitochondrial damage (Bobadilla et al., 2021; Mannucci et al., 2021), open new molecular pathways where antioxidants can play key roles. In this context, Costanzo et al., developed novel hydroxytyrosol-donepezil hybrids (Figure 1), and characterized their ROS scavenging, metal-chelating, and cytotoxic properties in vitro and in neuroblastoma cells. Among the donepezil hybrids, nitro hybrid HT2 and homovanillyl hybrid HT3a showed the most interesting antioxidant effects. The nitro Edited and reviewed by: Salvatore Salomone, University of Catania, Italy

PURPOSE:In this study, we evaluated the biological role of miRNA-31-5p in papillary thyroid cancer (PTC).METHODS:By using the real-time PCR, we measured miRNA-31-5p expression levels in 25 PTC tissues and in two human PTC cell lines (K1 and TPC-1). Then, K1 cells were transiently transfected with mirVana inhibitor or mirVana mimic to miRNA-31-5-p. Cell proliferation was determined by MTT and colony formation assays. The in vitro metastatic ability of thyroid cancer cells was evaluated by adhesion, migration and invasion assays. Epithelial mesenchymal transition (EMT) and Hippo pathway related gene and protein levels were evaluated by using the TaqMan™ Gene Expression Assays and western blot analysis, respectively.RESULTS:We found a significant increase of miR-31-5-p expression in tumor tissue and in K1 cells harboring the BRAF p.V600E mutation. Knockdown of miR-31-5p determined a reduction of cell proliferation, associated with a significant decrease in cell adhesion, migration and invasion properties. A downregulation of EMT markers and YAP/β-catenin axis was also observed.CONCLUSIONS:Our findings suggest that miRNA-31-5p acts as oncogenic miRNA in human thyrocytes and its overexpression may be involved in the BRAF-related tumorigenesis in PTCs, providing new understanding into its pathological role in PTC progression and invasiveness.

The manuscript describes the development of zein nanoparticles containing paclitaxel (PTX) and the bromo-and extra-terminal domain inhibitor (S)-tertbutyl2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno(3,2-f)(1,2,4)triazolo(4,3-a)(1,4)diazepin-6-yl)acetate (JQ1) together with their cytotoxicity on triple-negative breast cancer cells. The rationale of this association is that of exploiting different types of cancer cells as targets in order to obtain increased pharmacological activity with respect to that exerted by the single agents. Zein, a protein found in the endosperm of corn, was used as a biomaterial to obtain multidrug carriers characterized by mean sizes of ˂200 nm, a low polydispersity index (0.1–0.2) and a negative surface charge. An entrapment efficiency of ~35% of both the drugs was obtained when 0.3 mg/mL of the active compounds were used during the nanoprecipitation procedure. No adverse phenomena such as sedimentation, macro-aggregation or flocculation occurred when the nanosystems were heated to 37 °C. The multidrug nanoformulation demonstrated significant in vitro cytototoxic activity against MDA-MB-157 and MDA-MB-231 cancer cells by MTT-test and adhesion assay which was stronger than that of the compounds encapsulated as single agents. The results evidence the potential application of zein nanoparticles containing PTX and JQ1 as a novel nanomedicine.

Various natural compounds have been successfully tested for preventing or counteracting the toxic effects of exposure to heavy metals. In this study, we analyzed the effects of cadmium chloride (CdCl2) on immortalized, non-tumorigenic thyroid cells Nthy-ori-3-1. We investigated the molecular mechanism underlying its toxic action as well as the potential protective effect of quercetin against CdCl2-induced damage. CdCl2 suppressed cell growth in a dose- and time-dependent manner (IC50 value ~10 μM) associated with a decrease in levels of phospho-ERK. In addition, CdCl2 elicited an increase in reactive oxygen species (ROS) production and lipid peroxidation. A significant increase in GRP78, an endoplasmic reticulum (ER) stress-related protein, was also observed. Supplementation of quercetin counteracted the growth-inhibiting action of CdCl2 by recovering ERK protein phosphorylation levels, attenuating ROS overproduction, decreasing MDA content and reducing the expression of GRP78 in cells exposed to CdCl2. Thus, in addition to revealing the molecular effects involved in cadmium-induced toxicity, the present study demonstrated, for the first time, a protective effect of quercetin against cadmium-induced damages to normal thyroid cells.

Advances in nanotechnology have favored the development of novel colloidal formulations able to modulate the pharmacological and biopharmaceutical properties of drugs. The peculiar physico-chemical and technological properties of nanomaterial-based therapeutics have allowed for several successful applications in the treatment of cancer. The size, shape, charge and patterning of nanoscale therapeutic molecules are parameters that need to be investigated and modulated in order to promote and optimize cell and tissue interaction. In this review, the use of polymeric nanoparticles as drug delivery systems of anticancer compounds, their physico-chemical properties and their ability to be efficiently localized in specific tumor tissues have been described. The nanoencapsulation of antitumor active compounds in polymeric systems is a promising approach to improve the efficacy of various tumor treatments.

Purpose In this study, we investigated the profile of microRNAs (miRNAs) contained in exosomes secreted in the serum of patients with papillary thyroid cancer (PTC). Methods Exosome were isolated by adding ExoQuick Exosome Precipitation Solution. Dynamic light scattering (DLS) and western blotting analysis were used to ensure the quality of exosomes. The expression levels of miRNAs were investigated using custom-designed TaqMan Advanced miRNA Array Cards in the screening cohort and using specific TaqMan Advanced MicroRNA Assays in the validation cohort. Results We identified miR24-3p, miR146a-5p, miR181a-5p and miR382-5p with different expression levels in two different series of 56 and 58 PTC patients as compared with healthy controls. Significant differences in the expression of three PTC exosomal miRNAs, depending on the presence of lymph node metastasis, were detected in only one PTC series. When comparing the expression levels of some PTC-specific exosomal miRNAs with those of the same miRNAs circulating free of any encapsulation, we found a significant correlation for only miR24-3p, suggesting that only select miRNAs are secreted in exosomes. Conclusions Our findings demonstrate that four miRNAs are differently secreted in the exosomes of PTC patients, whereas no conclusive results were found to characterize PTCs with lymph node metastasis, suggesting caution in the use of circulating exosomal miRNA expression levels as lymph node metastasis biomarkers. Further investigation into the mechanisms governing miRNA secretion in tumor cells are required.

Passage of a drug across a biomembrane, such as a cell bilayer, vascular endothelium and bowel epithelium, the skin, the blood-brain barrier, is influenced by its physicochemical properties and characteristics of the biomembrane (Shinoda, 2016; Di Meo et al., 2016). Biomembranes contain cellular material in a closed space and provide a dynamic interface for interaction with the extracellular milieu. However, from a pharmaceutical perspective, biomembranes can also act as a barrier to drug delivery. Knowledge of these influences can provide us with a capability to localize drugs in specific body compartments by modifying the delivery systems, altering the route of administration, and incorporating the compartment-specific targeting moieties. With the goal of promoting drug permeation across a biomembrane, these techniques and approaches essentially hinge on the modulation of the interaction between the drug and the bilayer. This special issue is a collection of articles describing the state of the art pertaining to the use of biocompatible polymeric nanoparticles as drug carriers of bioactive compounds. The research articles discuss the in vivo fate of polymeric nanosystems in relation to the unique characteristics of the tumor microenvironment. A couple of other articles discuss the delivery of drugs through the cutaneous route. Torres et al. reviewed the nature of biobarriers and strategies to overcome them for the delivery of anticancer drugs. Specifically, the authors described nanocarriers composed of stimuli-responsive and self-assembling amphiphilic block copolymers to modulate the release of the payload. Exemplified by polylysine-cholate/PEG matrix to carry doxorubicin and deliver by pH stimuli (Zhu et al., 2012), such polymers are biocompatible and their compositions are tunable to match desired circulation persistence and target-oriented surface functionalization. Drug delivery by magnetic stimuli is another approach investigated by Li et al. The researchers employed an external magnetic field to induce localization of zolendronate-PLGA nanoparticles carrying superparamagnetic iron oxide in joints of a mouse model of osteolysis. They loaded these nanoparticles with curcumin to create dualtargeted nanoparticles and showed inhibition of NF-κB signaling and enhanced efficacy against polyethylene-induced osteolysis. Extending the application of stimuli-driven delivery of drugs, Oddone et al. engaged reactive oxygen species (ROS)-responsive mPEG-thioketal-melphalan prodrug for the potential treatment of glioblastoma. Although no in vivo efficacy studies were conducted, the investigators characterized the delivery system and tested it in cell culture. Thioketal linkage is sensitive to ROS and cleavage of thioketal bond releases melphalan from the micellar assembly of the drug-polymer conjugate. Because ROS levels are higher in cancer cells than in normal cells, such systems are expected to show selective cytotoxicity against cancer cells. In addition, the use of Edited and reviewed by: Salvatore Salomone, University of Catania, Italy

PURPOSE:In the search for novel effective compounds to use in thyroid cancer (TC) unresponsive to current treatment, attention has recently focused on plant-derived compounds with anticancer activity. In this review, we discuss the preclinical studies demonstrating phytochemical activity against thyroid cancer cells.RESULTS/CONCLUSIONS:In particular, we describe their antiproliferative properties or ability to re-induce iodine retention, thus supporting their potential use as single agents or adjuvants in radioiodine-resistant thyroid cancer treatment.