scholarly journals Molecular Insights and Emerging Strategies for Treatment of Metastatic Uveal Melanoma

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2761
Author(s):  
Fabiana Mallone ◽  
Marta Sacchetti ◽  
Alessandro Lambiase ◽  
Antonietta Moramarco
Keyword(s):  
Clinical Trials ◽  
Uveal Melanoma ◽  
Treatment Options ◽  
Survival Rates ◽  
Metastatic Tumor ◽  
Clinical Use ◽  
Future Perspectives ◽  
Diagnosis And Prognosis ◽  
Novel Treatment ◽  
Combinational Therapies

Uveal melanoma (UM) is the most common intraocular cancer. In recent decades, major advances have been achieved in the diagnosis and prognosis of UM allowing for tailored treatments. However, nearly 50% of patients still develop metastatic disease with survival rates of less than 1 year. There is currently no standard of adjuvant and metastatic treatment in UM, and available therapies are ineffective resulting from cutaneous melanoma protocols. Advances and novel treatment options including liver-directed therapies, immunotherapy, and targeted-therapy have been investigated in UM-dedicated clinical trials on single compounds or combinational therapies, with promising results. Therapies aimed at prolonging or targeting metastatic tumor dormancy provided encouraging results in other cancers, and need to be explored in UM. In this review, the latest progress in the diagnosis, prognosis, and treatment of UM in adjuvant and metastatic settings are discussed. In addition, novel insights into tumor genetics, biology and immunology, and the mechanisms underlying metastatic dormancy are discussed. As evident from the numerous studies discussed in this review, the increasing knowledge of this disease and the promising results from testing of novel individualized therapies could offer future perspectives for translating in clinical use.

scholarly journals Metastatic Uveal Melanoma: Treatment Strategies and Survival—Results from the Dutch Melanoma Treatment Registry

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1007 ◽  
Author(s):  
Anouk Jochems ◽  
Monique K. van der Kooij ◽  
Marta Fiocco ◽  
Maartje G. Schouwenburg ◽  
Maureen J. Aarts ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Uveal Melanoma ◽  
Treatment Options ◽  
Survival Rates ◽  
Real Life ◽  
Treatment Strategies ◽  
Stage Iv ◽  
Lactate Dehydrogenase Level ◽  
Stage Iv Disease ◽  
Melanoma Treatment

Uveal melanoma (UM) is the most common primary intraocular tumor in adults. Up to 50% of UM patients will develop metastases. We present data of 175 metastatic UM patients diagnosed in the Netherlands between July 2012 and March 2018. In our cohort, elevated lactate dehydrogenase level (LDH) is an important factor associated with poorer survival (Hazard Ratio (HR) 9.0, 95% Confidence Interval (CI) 5.63–14.35), and the presence of liver metastases is negatively associated with survival (HR 2.09, 95%CI 1.07–4.08). We used data from the nation-wide Dutch Melanoma Treatment Registry (DMTR) providing a complete overview of the location of metastases at time of stage IV disease. In 154 (88%) patients, the liver was affected, and only 3 patients were reported to have brain metastases. In 63 (36%) patients, mutation analysis was performed, showing a GNA11 mutation in 28.6% and a GNAQ mutation in 49.2% of the analyzed patients. In the absence of standard care of treatment options, metastatic UM patients are often directed to clinical trials. Patients participating in clinical trials are often subject to selection and usually do not represent the entire metastatic UM population. By using our nation-wide cohort, we are able to describe real-life treatment choices made in metastatic UM patients and 1-year survival rates in selected groups of patients.

Új lehetőségek a refrakter és relabált Hodgkin-lymphomás betegek kezelésében

2015 ◽  
Vol 156 (45) ◽  
pp. 1824-1833 ◽  
Author(s):  
Árpád Illés ◽  
Ádám Jóna ◽  
Zsófia Simon ◽  
Miklós Udvardy ◽  
Zsófia Miltényi
Keyword(s):  
Stem Cell ◽  
Hodgkin Lymphoma ◽  
Treatment Options ◽  
Survival Rates ◽  
Relapse Free Survival ◽  
Term Survival ◽  
Free Survival ◽  
Novel Treatment ◽  
Refractory Hodgkin Lymphoma

Introduction: Hodgkin lymphoma is a curable lymphoma with an 80–90% long-term survival, however, 30% of the patients develop relapse. Only half of relapsed patients can be cured with autologous stem cell transplantation. Aim: The aim of the authors was to analyze survival rates and incidence of relapses among Hodgkin lymphoma patients who were treated between January 1, 1980 and December 31, 2014. Novel therapeutic options are also summarized. Method: Retrospective analysis of data was performed. Results: A total of 715 patients were treated (382 men and 333 women; median age at the time of diagnosis was 38 years). During the studied period the frequency of relapsed patients was reduced from 24.87% to 8.04%. The numbers of autologous stem cell transplantations was increased among refracter/relapsed patients, and 75% of the patients underwent transplantation since 2000. The 5-year overall survival improved significantly (between 1980 and 1989 64.4%, between 1990 and 1999 82.4%, between 2000 and 2009 88.4%, and between 2010 and 2014 87.1%). Relapse-free survival did not change significantly. Conclusions: During the study period treatment outcomes improved. For relapsed/refractory Hodgkin lymphoma patients novel treatment options may offer better chance for cure. Orv. Hetil., 2015, 156(45), 1824–1833.

scholarly journals Nanobiosensors for Non-Amyloidbeta-Tau Biomarkers as Advanced Reporters of Alzheimer’s Disease

Diagnostics ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 913
Author(s):  
Le Minh Tu Phan ◽  
Thi Xoan Hoang ◽  
Thuy Anh Thu Vo ◽  
Jae Young Kim ◽  
Sang-Myung Lee ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Therapeutic Response ◽  
Accurate Diagnosis ◽  
Clinical Severity ◽  
Future Perspectives ◽  
Comprehensive Management ◽  
Diagnosis And Prognosis ◽  
Sensitivity Specificity

Emerging nanomaterials providing benefits in sensitivity, specificity and cost-effectiveness are being widely investigated for biosensors in the application of Alzheimer’s disease (AD) diagnosis. Core biomarkers amyloid-beta (Aβ) and Tau have been considered as key neuropathological hallmarks of AD. However, they did not sufficiently reflect clinical severity and therapeutic response, proving the difficulty of the Aβ- and Tau-targeting therapies in clinical trials. In recent years, there has still been a shortage of sensors for non-Aβ-Tau pathophysiological biomarkers that serve as advanced reporters for the early diagnosis of AD, predict AD progression, and monitor the treatment response. Nanomaterial-based sensors measuring multiple non-Aβ-Tau biomarkers could improve the capacity of AD progression characterization and supervised treatment, facilitating the comprehensive management of AD. This is the first review to principally represent current nanobiosensors for non-Aβ-Tau biomarker and that strategically deliberates future perspectives on the merit of non-Aβ-Tau biomarkers, in combination with Aβ and Tau, for the accurate diagnosis and prognosis of AD.

scholarly journals The Emerging Role of c-Met in Carcinogenesis and Clinical Implications as a Possible Therapeutic Target

2022 ◽  
Vol 2022 ◽  
pp. 1-12
Author(s):  
Antonio Faiella ◽  
Ferdinando Riccardi ◽  
Giacomo Cartenì ◽  
Martina Chiurazzi ◽  
Livia Onofrio
Keyword(s):  
Clinical Trials ◽  
Epithelial Mesenchymal Transition ◽  
Target Therapy ◽  
Treatment Options ◽  
Survival Rates ◽  
Response To Treatment ◽  
Tyrosine Kinase Receptor ◽  
Mesenchymal Transition ◽  
Surface Receptors ◽  
Clinical Consequences

Background. c-MET is a receptor tyrosine kinase receptor (RTK) for the hepatocyte growth factor (HGF). The binding of HGF to c-MET regulates several cellular functions: differentiation, proliferation, epithelial cell motility, angiogenesis, and epithelial-mesenchymal transition (EMT). Moreover, it is known to be involved in carcinogenesis. Comprehension of HGF-c-MET signaling pathway might have important clinical consequences allowing to predict prognosis, response to treatment, and survival rates based on its expression and dysregulation. Discussion. c-MET represents a useful molecular target for novel engineered drugs. Several clinical trials are underway for various solid tumors and the development of new specific monoclonal antibodies depends on the recent knowledge about the definite c-MET role in each different malignance. Recent clinical trials based on c-MET molecular targets result in good safety profile and represent a promising therapeutic strategy for solid cancers, in monotherapy or in combination with other target drugs. Conclusion. The list of cell surface receptors crosslinking with the c-MET signaling is constantly growing, highlighting the importance of this pathway for personalized target therapy. Research on the combination of c-MET inhibitors with other drugs will hopefully lead to discovery of new effective treatment options.

scholarly journals Clinical Trials in Metastatic Uveal Melanoma: Current Status

2020 ◽  
Vol 6 (6) ◽  
pp. 381-387
Author(s):  
Tamara A. Sussman ◽  
Pauline Funchain ◽  
Arun Singh
Keyword(s):  
Clinical Trials ◽  
Targeted Therapy ◽  
Uveal Melanoma ◽  
Oncolytic Virus ◽  
Survival Rates ◽  
Standard Of Care ◽  
Therapeutic Benefit ◽  
Review Article ◽  
Current Status ◽  
Melanoma Prognosis

<b><i>Background:</i></b> Uveal melanoma is a rare subtype of melanoma. Prognosis and survival rates for patients with metastatic uveal melanoma remain poor. No current FDA-approved standard of care therapy is available for patients with metastatic uveal melanoma. Thus, clinical trials are essential for the development of new therapies and to provide patients hope for improved survival and outcomes. <b><i>Summary:</i></b> In this article, we review clinical trials identified on the database https://clinicaltrials.gov that are open and enrolling patients with metastatic uveal melanoma as of November 26, 2019. This search produced 17 active trials involving liver-directed therapy, CNS-directed therapy, and systemic therapy with immunotherapy, targeted therapy, or oncolytic virus therapy. Here, we discuss liver and CNS-directed therapy as well as systemic targeted therapy and oncolytic virus therapy. Immunotherapy clinical trials are discussed in a companion review article by Dr. Marlana Orloff. <b><i>Key Messages:</i></b> Various novel therapeutic targets and immunomodulatory approaches are on the horizon for patients with metastatic uveal melanoma and may yield incremental therapeutic benefit. Selecting a clinical trial must be individualized and made jointly with the patient and his/her oncologist.

scholarly journals New Treatment Options for Advanced Gastroesophageal Tumours: Mature for the Current Practice?

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 301
Author(s):  
Hannah Christina Puhr ◽  
Matthias Preusser ◽  
Gerald Prager ◽  
Aysegül Ilhan-Mutlu
Keyword(s):  
Clinical Trials ◽  
Targeted Therapy ◽  
Targeted Therapies ◽  
Current Practice ◽  
Treatment Options ◽  
Novel Agents ◽  
Novel Treatment ◽  
New Treatment ◽  
Current Impact

Several clinical trials attempted to identify novel treatment options for advanced gastroesophageal tumours in first, second and further lines. Although results of targeted therapy regimens were mainly disappointing, novel immunotherapy agents showed promising activity, which led to their approval in second and third lines in many countries. This review focuses on the results of recent clinical trials investigating novel agents including targeted therapies, immunotherapy components and chemotherapies and discuss their current impact as well as current approval status on the treatment armamentarium of advanced gastroesophageal tumours.

scholarly journals INNV-20. A SYSTEMATIC REVIEW OF TUMOR TREATING FIELDS THERAPY FOR PRIMARY FOR RECURRENT AND GLIOBLASTOMA

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi134-vi135
Author(s):  
Pavan Shah ◽  
Taija White ◽  
Carrie Price ◽  
Debraj Mukherjee
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Electric Fields ◽  
Treatment Modality ◽  
Randomized Clinical Trials ◽  
Treatment Options ◽  
Recurrent Glioblastoma ◽  
Skin Reactions ◽  
Tumor Treating Fields ◽  
Novel Treatment

Abstract BACKGROUND Glioblastoma is an aggressive primary central nervous system malignancy with poor prognosis and limited treatment options. Tumor treating fields (TTFs) are a novel treatment modality utilizing alternating electric fields that have demonstrated promise in randomized clinical trials for primary and recurrent glioblastomas. In addition to these studies, a multitude of smaller investigations have been performed examining their efficacy in a variety of combination therapies. This systematic review of available literature aims to summarize and evaluate the efficacy and safety of TTFs for primary and recurrent glioblastoma patients. METHODS A systematic review of the literature was performed according to PRISMA guidelines from database inception through 2/27/2019. Databases queried include PubMed, Embase, Cochrane, Scopus, Web of Science, and ClinicalTrials.gov. 856 unique studies were initially identified in this search, 9 of which met final inclusion criteria. 2 authors independently performed the screening and data extraction of the studies. RESULTS Excluding historical controls, 1569 patients were identified in these studies, 1191 of which received TTFs therapy. TTFs were evaluated in single-arm clinical trials (n = 2), randomized clinical trials (n = 2), and retrospective studies (n = 5). These 9 studies are presented based on treatments provided, baseline patient characteristics, and patient outcomes. No adverse events appear to be associated with TTFs other than adverse skin reactions. Given the heterogeneity in the presented studies, a quantitative meta-analysis was not performed. CONCLUSIONS TTFs are a novel treatment modality that have demonstrated safety and efficacy in a number of settings and study designs. However, further investigation is needed to continue characterizing treatment outcomes and assessing TTFs interactions with various drug regimens.

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