Novel therapeutic strategies and targets in advanced uveal melanoma

Purpose of review Currently, there are no U.S. Food and Drug Administration-approved or effective treatment options for advanced-stage uveal melanoma. In this article, we focus on therapeutic targets in pathways/mechanisms associated with common mutations in uveal melanoma. We review the challenges associated with targeting of these pathways and novel treatment strategies. Recent findings Common mutations that promote uveal melanoma initiation and progression include alterations in G protein subunit alpha q/11 (GNAQ/GNA11) and breast cancer gene 1-associated protein 1 (BAP1). Mutant GNAQ/GNA11 induces constitutive activation of tumorigenic pathways such as extracellular signal-regulated kinase (ERK)1/2 and yes-associated protein. Inhibition of mitogen-activated protein kinase kinase (MEK) downstream of ERK1/2, however, was shown in trials to have limited clinical benefit. Recent reports suggested that combination therapies of MEK inhibition and modulators of mechanisms of drug resistance may improve tumor responses to MEK inhibitors. BAP1 has been shown to be involved in modulating chromatin dynamics and deubiquitination of proteins. Hence, epigenetic inhibitors are being investigated in BAP1 mutant uveal melanoma. However, other functions of BAP1, such as in DNA damage repair and cell cycle regulation, indicate additional targets for treatment of BAP1 mutant uveal melanoma. In addition, the frequent delayed development of uveal melanoma macrometastases is likely due to ...
Source: Current Opinion in Oncology - Category: Cancer & Oncology Tags: MELANOMA AND OTHER SKIN NEOPLASMS: Edited by Reinhard Dummer Source Type: research

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FINDINGSUCLA researchers found that nearly all people diagnosed with uveal melanoma had a number of unmet psychological and health information needs, particularly during the first three months after their diagnoses. The study is the first to examine long-term supportive care needs among patients with this disease, and suggested there are more acute needs among people with uveal melanoma than people with other cancers. Social and psychological circumstances that affect these patients, such as personality factors, the social support they receive and the size of their social network, contributed more to a greater need for sup...
Source: UCLA Newsroom: Health Sciences - Category: Universities & Medical Training Source Type: news
Abstract Familial risks of breast cancer (BC) are well established but whether BC clusters with other, i.e. discordant, cancers is less certain but of interest for the identification of common genetic and possible environmental factors contributing to a general cancer susceptibility. We apply a novel approach to search for familial associations of BC with other (discordant) cancers based on the Swedish Family‐Cancer Database. Relative risks (RRs) were calculated for BC in families with increasing numbers of patients with discordant cancer X, and conversely, familial RRs for cancer X in families with increasing numbers of...
Source: International Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Research Article Source Type: research
ConclusionsIn summary, we generated a tumor-type independent ATRA-sensitivity predictor which consists of a restricted number of genes and has the potential to be applied in the clinics. Identification of the tumor types that are likely to be generally sensitive to the action of ATRA paves the way to the design of clinical studies in the context of these diseases. In addition, ATRA-21 may represent an important diagnostic tool for the selection of individual patients who may benefit from ATRA-based therapeutic strategies also in tumors characterized by lower average sensitivity.
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
ConclusionsBreast cancer is most common in development of metastatic tumors. Medical history data, clinical and instrumental findings are informative to suggest malignancy in orbit, requiring the need for morphological verification of the diagnosis for adequate therapy.
Source: Acta Ophthalmologica - Category: Opthalmology Authors: Tags: Abstracts from the 2016 European Association for Vision and Eye Research Conference Source Type: research
CONCLUSIONSWith greatly limited amounts of data, PBT offers promising cost‐effectiveness for pediatric brain tumors, well‐selected breast cancers, locoregionally advanced NSCLC, and high‐risk head/neck cancers. Heretofore, it has not been demonstrated that PBT is cost‐effective for prostate cancer or early stage NSCLC. Careful patient selection is absolutely critical to assess cost‐effectiveness. Together with increasing PBT availability, clinical trial evidence, and ongoing major technological improvements, cost‐effectiveness data and conclusions from this analysis could change rapidly. Cancer 2016. © 201...
Source: Cancer - Category: Cancer & Oncology Authors: Tags: Review Article Source Type: research
Conclusion: Interventional oncological techniques play a role in patients with liver-dominant metastases.Viszeralmedizin 2015;31:406-413
Source: Viszeralmedizin - Category: Gastroenterology Source Type: research
Authors: Pin YK, Khoo K, Tham M, Karwai T, Hwee TC, Puaux AL, Phua ML, Kato M, Angeli V, Abastado JP Abstract Resection of infiltrated tumor-draining lymph nodes (TDLNs) is a standard practice for the treatment of several cancers including breast cancer and melanoma. However, many randomized prospective trials have failed to show convincing clinical benefits associated with LN removal and the role of TDLNs in cancer dissemination is poorly understood. Here, we found in a well-characterized spontaneous mouse model of uveal melanoma that the growth of the primary tumor was accompanied by increased lymphangiogenesis a...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
Mutations in genes encoding proteins involved in RNA splicing have been found to occur at relatively high frequencies in several tumour types including myelodysplastic syndromes, chronic lymphocytic leukaemia, uveal melanoma, pancreatic cancer and at lower frequencies in breast cancer. To investigate whether dysfunction in RNA splicing is implicated in the pathogenesis of breast cancer, we performed a re-analysis of published exome and whole genome sequencing data. This analysis revealed that mutations in spliceosomal component genes occurred in 5.6% of unselected breast cancers, including hotspot mutations in the SF3B1 ge...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Genomics and Target Discovery Source Type: research
Wei-Heng Kao, Yi-Liang Shen, Ji-Hong HongBiomedical Journal 2015 38(5):391-398The potential benefits of proton therapy have been established in pediatric cancer, skull base tumor, uveal melanoma, and other types of cancers. Western and Asian countries, however, have differences in the pattern of cancer incidence; this leads to the difference in patient demographics for proton therapy. Furthermore, the advancement of the scanning beam technique in proton therapy greatly expands the capability of proton therapy in disease sites with great complexity. In this review, we focus on the cancers with high incidence in Taiwan, base...
Source: Biomedical Journal - Category: Biomedical Science Authors: Source Type: research
by Christopher DeBoever, Emanuela M. Ghia, Peter J. Shepard, Laura Rassenti, Christian L. Barrett, Kristen Jepsen, Catriona H. M. Jamieson, Dennis Carson, Thomas J. Kipps, Kelly A. Frazer Mutations in the splicing factor SF3B1 are found in several cancer types and have been associated with various splicing defects. Using transcriptome sequencing data from chronic lymphocytic leukemia, breast cancer and uveal melanoma tumor samples, we show that hundreds of cryptic 3’ splice sites (3’SSs) are used in cancers with SF3B1 mutations. We define the necessary sequence context for the observed cryptic 3’ SSs and...
Source: PLoS Computational Biology - Category: Biology Authors: Source Type: research
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