Targeting Integrins with Radiolabeled RGD Analogues for Radiotheranostics of Metastatic Radioactive Iodine Nonresponsive Thyroid Cancer: New Avenues in Personalized Medicine.
Ontology highlight
ABSTRACT:
SUBMITTER: Klubo-Gwiezdzinska J
PROVIDER: S-EPMC7187961 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:ObjectiveCurrent diagnosis of radioactive iodine (RAI)-refractory (RAIR) differentiated thyroid cancer (DTC) is based on the imaging technique, which is of a high cost. Serum thyroglobulin (Tg) is a sensitive and easily obtained biomarker. Hence, we aimed to assess the predicting value of quantitative response of Tg in earlier identifying the RAIR-DTC with pulmonary metastasis.Patients and methodsPulmonary metastatic DTC patients who underwent total or near-total thyroidectomy and at least two times of RAI therapy were included in this study. The pre-ablative stimulated Tg at the first and second RAI therapy were defined as pstim-Tg1 and pstim-Tg2, while the suppressed Tg before and after the second RAI therapy were designated sup-Tg1 and sup-Tg2. The predicted value of pstim-Tg2/Tg1 and sup-Tg2/Tg1 ratio were detected using the receiver operating characteristic (ROC) curve and logistic regression analyses.ResultsTotally 115 patients were involved in this study. ROC curves showed a cut-off value of 0.544 for pstim-Tg2/ pstim-Tg1 in detecting RAIR, with a sensitivity of 0.9 and specificity of 0.477, and an area under the curve (AUC) of 0.744. Similarly, the cut-off of sup-Tg2/ sup-Tg1 was 0.972, with a sensitivity of 0.733 and specificity of 0.935, and AUC of 0.898. Univariate analysis illustrated that age, tumor size, pstim-Tg2/Tg1, sup-Tg2/ sup-Tg1 and BRAFV600E mutation were eligible to predict RAIR. While from multivariate analysis, only age, pstim-Tg2/Tg1, sup-Tg2/ sup-Tg1 and BRAFV600E mutation were verified to be the independent predictive factors.ConclusionThe quantitative Tg response was encouraging in identifying RAIR-DTC with pulmonary metastasis. Age, BRAFV600E mutation and Tg response were independent predictors in predicting RAIR-DTC.
| S-EPMC5509138 | biostudies-literature
Project description:Iodine-resistant cancers account for the vast majority of thyroid related mortality and, until recently, there were limited therapeutic options. However, over the last decade our understanding of the molecular foundation of thyroid function and carcinogenesis has driven the development of many novel therapeutics. These include FDA approved tyrosine kinase inhibitors and small molecular inhibitors of VEGFR, BRAF, MEK, NTRK and RET, which collectively have significantly changed the prognostic outlook for this patient population. Some therapeutics can re-sensitize de-differentiated cancers to iodine, allowing for radioactive iodine treatment and improved disease control. Remarkably, there is now an FDA approved treatment for BRAF-mutated patients with anaplastic thyroid cancer, previously considered invariably and rapidly fatal. The treatment landscape for iodine-resistant thyroid cancer is changing rapidly with many new targets, therapeutics, clinical trials, and approved treatments. We provide an up-to-date review of novel therapeutic options in the treatment of iodine-resistant thyroid cancer.
| S-EPMC8321684 | biostudies-literature
Project description:Integrins are key regulators of communication between cells and with their microenvironment. Eight members of the integrin superfamily recognize the tripeptide motif Arg-Gly-Asp (RGD) within extracelluar matrix (ECM) proteins. These integrins constitute an important subfamily and play a major role in cancer progression and metastasis via their tumor biological functions. Such transmembrane adhesion and signaling receptors are thus recognized as promising and well accessible targets for novel diagnostic and therapeutic applications for directly attacking cancer cells and their fatal microenvironment. Recently, specific small peptidic and peptidomimetic ligands as well as antibodies binding to distinct integrin subtypes have been developed and synthesized as new drug candidates for cancer treatment. Understanding the distinct functions and interplay of integrin subtypes is a prerequisite for selective intervention in integrin-mediated diseases. Integrin subtype-specific ligands labelled with radioisotopes or fluorescent molecules allows the characterization of the integrin patterns in vivo and later the medical intervention via subtype specific drugs. The coating of nanoparticles, larger proteins, or encapsulating agents by integrin ligands are being explored to guide cytotoxic reagents directly to the cancer cell surface. These ligands are currently under investigation in clinical studies for their efficacy in interference with tumor cell adhesion, migration/invasion, proliferation, signaling, and survival, opening new treatment approaches in personalized medicine.
| S-EPMC5615331 | biostudies-literature
Project description:Persistent or recurrent hyperthyroidism after treatment with radioactive iodine (RAI) is common and many patients require either additional doses or surgery before they are cured. The purpose of this study was to identify patterns and predictors of failure of RAI in patients with hyperthyroidism.We conducted a retrospective review of patients treated with RAI from 2007 to 2010. Failure of RAI was defined as receipt of additional dose(s) and/or total thyroidectomy. Using a Cox proportional hazards model, we conducted univariate analysis to identify factors associated with failure of RAI. A final multivariate model was then constructed with significant (p < 0.05) variables from the univariate analysis.Of the 325 patients analyzed, 74 patients (22.8 %) failed initial RAI treatment, 53 (71.6 %) received additional RAI, 13 (17.6 %) received additional RAI followed by surgery, and the remaining 8 (10.8 %) were cured after thyroidectomy. The percentage of patients who failed decreased in a stepwise fashion as RAI dose increased. Similarly, the incidence of failure increased as the presenting T3 level increased. Sensitivity analysis revealed that RAI doses <12.5 mCi were associated with failure while initial T3 and free T4 levels of at least 4.5 pg/mL and 2.3 ng/dL, respectively, were associated with failure. In the final multivariate analysis, higher T4 (hazard ratio [HR] 1.13; 95 % confidence interval [CI] 1.02-1.26; p = 0.02) and methimazole treatment (HR 2.55; 95 % CI 1.22-5.33; p = 0.01) were associated with failure.Laboratory values at presentation can predict which patients with hyperthyroidism are at risk for failing RAI treatment. Higher doses of RAI or surgical referral may prevent the need for repeat RAI in selected patients.
| S-EPMC4330099 | biostudies-literature
Project description:Until recently, no truly effective treatment options have existed for patients with radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC), a serious disease with poor prognosis. In November 2013, the targeted multikinase inhibitor, sorafenib, was approved for use in these patients based on substantially improved progression-free survival compared with placebo. A number of other targeted agents, including lenvatinib, are being investigated in phase II and phase III trials. With the advent of these new treatment options, practitioners are faced with making important decisions in determining which patients are candidates for systemic treatment and the optimal timing for treatment initiation. Since patients may remain asymptomatic for a protracted period of time, tumor size and growth rate are the primary considerations for making these choices. Proactive management of side effects is also critical in optimizing the effectiveness of treatment. Here we review targeted systemic agents that are either in use or are under investigation for RAI-refractory DTC and provide recommendations on the rationale for initiating systemic treatment and on managing adverse events. Four illustrative case studies are provided.
| S-EPMC4206652 | biostudies-literature
Project description:Radioactive iodine (RAI) is a key component in the treatment of differentiated thyroid cancer. RAI has been recommended more selectively in recent years as guidelines evolve to reflect risks and utility in certain patient subsets. In this study we sought to evaluate the survival impact of radioactive iodine in specific thyroid cancer subgroups. Nationwide retrospective cohort study of patients using the National Cancer Database (NCDB) from 2004 to 2012 and Surveillance, Epidemiology, and End Results (SEER) database from 1992 to 2009 examining patients with differentiated thyroid cancer treated with or without RAI. Primary outcomes included all-cause mortality (NCDB and SEER), and cancer-specific mortality (SEER). Cox multivariate survival analyses were applied to each dataset, and in 135 patient subgroups based on clinical and non-clinical parameters. A total of 199,371 NCDB and 77,187 SEER patients were identified. RAI was associated with improved all-cause mortality (NCDB: RAI hazard ratio (HR) 0.55, P < 0.001; SEER: HR 0.64, P < 0.001); and cancer-specific mortality (SEER: HR 0.82, P = 0.029). Iodine therapy showed varied efficacy within each subgroup. Patients with high-risk disease experienced the greatest benefit in all-cause mortality, followed by intermediate-risk, then low-risk subgroups. Regarding cancer-specific mortality, radioactive iodine therapy was protective in high-risk patients, but did not achieve statistical significance in most intermediate-risk subgroups. Low-risk T1a subgroups demonstrated an increased likelihood of cancer-specific mortality with iodine therapy. The efficacy of RAI in patients with differentiated thyroid cancer varies by disease severity. A negative cancer-specific survival association was identified in patients with T1a disease. These findings warrant further evaluation with prospective studies.
| S-EPMC6994333 | biostudies-literature
Project description:Efficient and cost-effective removal of radioactive iodine (radioiodine) from radioactive contaminated water has become a crucial task, following nuclear power plant disasters. Several materials for removing radioiodine have been reported in the literature. However, most of these materials exhibit some limitations, such as high production cost, slow adsorption kinetics, and poor adsorption capacity. Herein, we present silver/iron oxide nanocomposites (Ag/Fe3O4) for the efficient and specific removal of iodine anions from contaminated water. The Ag/Fe3O4 were synthesized using a modified method and characterized via scanning electron microscopy, transmission electron microscopy, and X-ray diffraction analyses. This adsorbent showed a high adsorption capacity for iodine anions (847 mg/g of the adsorbent) in pure water. Next, Ag/Fe3O4 was applied to the removal of radioiodine, and high removal efficiencies were observed in water. In addition, its desalination capacity was retained in the presence of competitive ions and varied pH. After the adsorption process, Ag/Fe3O4 was easily removed from the water by applying an external magnetic field. Moreover, the same operation can be repeated several times without a significant decrease in the performance of Ag/Fe3O4. Therefore, it is expected that the findings presented in this study will offer a new method for desalinating radioiodine in various aqueous media.
| S-EPMC7996965 | biostudies-literature
Project description:It remains controversial whether papillary thyroid cancer (PTC) patients with low- to intermediate-risk disease should receive radioactive iodine (RAI) after total thyroidectomy (TT). We aim to identify those who might benefit from RAI treatment in PTC patients with cervical nodal metastasis after TT. Patients were divided into TT and TT+RAI groups from the Surveillance, Epidemiology, and End Results (SEER) database (2004-2018). Overall survival (OS) and cancer-specific survival (CSS) were compared, and propensity score matching (PSM) was performed between groups. A total of 15,179 patients were enrolled, including 3,387 (22.3%) who underwent TT and 11,792 (77.7%) who received TT+RAI. The following characteristics were more likely to present in the TT+RAI group: multifocality, capsular extension, T3, N1b, and more metastatic cervical lymph nodes. RAI was associated with better OS in low- to intermediate-risk PTC patients in the multivariate Cox regression model. The subgroup analysis showed that RAI predicted better OS in patients ≥55 years, American Joint Committee on Cancer (AJCC) stage II, and capsular extension with a hazard ratio (HR) (95% CI) of 0.57 (0.45-0.72), 0.57 (0.45-0.72), and 0.68 (0.51-0.91), respectively. However, RAI failed to improve the prognoses of patients with age <55 years, AJCC stage I, PTC ≤1 cm, and capsular invasion. In the PSM cohort with 3,385 paired patients, TT+RAI treatment predicted better OS compared with TT alone. In addition, TT+RAI predicted better OS in patients with metastatic cervical lymph nodes ≥2, multifocality, extracapsular extension, and American Thyroid Association (ATA) intermediate risk. In conclusion, RAI was associated with better OS in low- to intermediate-risk PTC patients with age ≥55 years, multifocality, extrathyroidal extension, and ATA intermediate risk. However, the survival benefit from RAI may be limited in patients with AJCC stage I, PTC ≤1 cm, unifocality, capsular invasion, and ATA low-risk diseases; these patients even showed pathological cervical lymph node metastasis.
| S-EPMC9402902 | biostudies-literature
Project description:Objective: To evaluate the efficacy and treatment rationale of Hürthle cell carcinoma (HCC) following a patient with progressive and metastatic HCC. HCC was recently shown to harbor a distinct genetic make-up and the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kiase (PI3K)/AKT signaling pathways are potential targets for anti-cancer agents in the management of recurrent HCC. The presence or absence of gene variants can give a rationale for targeted therapies that could be made available in the context of drug repurposing trials. Methods: Treatment included everolimus, sorafenib, nintedanib, lenvatinib, and panitumumab. Whole genome sequencing (WGS) of metastatic tumor material obtained before administration of the last drug, was performed. We subsequently evaluated the rationale and efficacy of panitumumab in thyroid cancer and control cell lines after epidermal growth factor (EGF) stimulation and treatment with panitumumab using immunofluorescent Western blot analysis. EGF receptor (EGFR) quantification was performed using flow cytometry. Results: WGS revealed a near-homozygous genome (NHG) and a somatic homozygous TSC1 variant, that was absent in the primary tumor. In the absence of RAS variants, panitumumab showed no real-life efficacy. This might be explained by high constitutive AKT signaling in the two thyroid cancer cell lines with NHG, with panitumumab only being a potent inhibitor of pEGFR in all cancer cell lines tested. Conclusions: In progressive HCC, several treatment options outside or inside clinical trials are available. WGS of metastatic tumors might direct the timing of therapy. Unlike other cancers, the absence of RAS variants seems to provide insufficient justification of single-agent panitumumab administration in HCC cases harboring a near-homozygous genome.
| S-EPMC6721552 | biostudies-literature
Project description:Patients with well-differentiated thyroid cancer, especially papillary thyroid cancer (PTC), are treated with surgical resection of the thyroid gland. This is followed by post-operative radioactive iodine (I131), resulting in total thyroid ablation. Unfortunately, about 15-33% of PTC patients are unable to take up I131, limiting further treatment options. The aim of our study was to develop a cancer organoid model with the potential for pre-treatment diagnosis of these I131-resistant patients. PTC tissue from thirteen patients was used to establish a long-term organoid model. These organoids showed a self-renewal potential for at least five passages, suggesting the presence of cancer stem cells. We demonstrated that thyroid specific markers, a PTC marker, and transporters/receptors necessary for iodine uptake and thyroid hormone production were expressed on a gene and protein level. Additionally, we cultured organoids from I131-resistant PTC material from three patients. When comparing PTC organoids to radioactive iodine (RAI)-refractory disease (RAIRD) organoids, a substantial discordance on both a protein and gene expression level was observed, indicating a treatment prediction potential. We showed that patient-derived PTC organoids recapitulate PTC tissue and a RAIRD phenotype. Patient-specific PTC organoids may enable the early identification of I131-resistant patients, in order to reduce RAI overtreatment and its many side effects for thyroid cancer patients.
| S-EPMC7692469 | biostudies-literature