Response of patients with metastatic uveal melanoma to combined treatment with fotemustine and sorafenib

A, Niederkorn; Wackernagel, Werner; Artl, Monika; Schwantzer, Gerold; Aigner, Birgit; Richtig, Erika

doi:10.1111/aos.12432

Cited by 12 publications

(10 citation statements)

References 6 publications

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“…Uveal melanoma (UM) is a rare tumor of the eye that gives rise to metastases, especially in the liver, and is deadly in about one half of cases. Metastases are insensitive to chemotherapy, thereby leading to a high mortality rate [ 1 , 2 , 3 ]. Mutually-exclusive mutations in the GNAQ or GNA11 genes, which encode signaling proteins associated with G-protein-coupled receptors, are specific drivers of UM [ 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

Potential Onco-Suppressive Role of miR122 and miR144 in Uveal Melanoma through ADAM10 and C-Met Inhibition

Amaro

Croce

Ferrini

et al. 2020

Cancers

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Uveal melanoma (UM) is a rare tumor of the eye that leads to deadly metastases in about half of the patients. ADAM10 correlates with c-Met expression in UM and high levels of both molecules are related to the development of metastases. MiR122 and miR144 modulate ADAM10 and c-Met expression in different settings. We hypothesized a potential onco-suppressive role for miR122 and miR144 through modulation of ADAM10 and c-Met in UM. We analyzed the UM Cancer Genome Atlas data portal (TCGA) dataset, two other cohorts of primary tumors and five human UM cell lines for miR122 and miR144 expression by miR microarray, RT-qPCR, Western blotting, miR transfection and luciferase reporter assay. Our results indicate that miR122 and miR144 are expressed at low levels in the UM cell lines and in the TCGA UM dataset and were down-modulated in a cohort of seven UM samples, compared to normal choroid. Both miR122 and miR144 directly targeted ADAM10 and c-Met. Overexpression of miR122 and miR144 led to reduced expression of ADAM10 and c-Met in the UM cell lines and impaired cell proliferation, migration, cell cycle and shedding of c-Met ecto-domain. Our results show that miR122 and miR144 display an onco-suppressive role in UM through ADAM10 and c-Met modulation.

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Section: Introductionmentioning

confidence: 99%

Potential Onco-Suppressive Role of miR122 and miR144 in Uveal Melanoma through ADAM10 and C-Met Inhibition

Amaro

Croce

Ferrini

et al. 2020

Cancers

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“…Another study combining sorafenib with fotemustine also showed a partial response or stable disease in 37.5% of the patients . A phase II trial of sorafenib alone revealed stable disease at 24 weeks in 31.2% of patients .…”

Section: Preclinical Approachesmentioning

confidence: 97%

“…94 Another study combining sorafenib with fotemustine also showed a partial response or stable disease in 37.5% of the patients. 95 A phase II trial of sorafenib alone revealed stable disease at 24 weeks in 31.2% of patients. 96 Although it seems that sorafenib promotes the stabilization of the disease, it failed to improve OS of metastatic UM patients.…”

Section: Targeted Therapymentioning

confidence: 99%

“…The MAPK pathway, which is frequently upregulated in UM, can be inhibited by the multikinase inhibitor sorafenib at the level of Raf kinases . This inhibitor also decreases cell growth and angiogenesis via inhibition of several receptor tyrosine kinases including the vascular endothelial growth factor receptor (VEGFR) and the platelet‐derived growth factor receptor (PDGFR) . However, a phase II study of sorafenib in combination with carboplatin and paclitaxel was unable to prove significant efficacy (objective RR [ORR] = 0% [95% CI: 0–14%]) even though minor tumor responses and prolonged stable disease were observed in a minority of patients.…”

Section: Preclinical Approachesmentioning

confidence: 99%

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Recent advances in uveal melanoma treatment

Álvarez‐Rodríguez

Latorre

Posch

et al. 2017

Medicinal Research Reviews

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Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Recent advances in the understanding of molecular characteristics helped to determine which tumors are most likely to progress. About 50% of patients carrying genetic alterations such as chromosomal aberrations and mutations are at significant risk for metastatic disease of which the majority will succumb to UM within few months. Currently, there is no effective treatment for metastatic uveal melanoma, and we hope this review will encourage researchers and clinicians to work to find a better standard of care.In this article we provide a comprehensive overview of the molecular framework of UM, highlighting the most common mutations involved in this kind of cancer. It also covers the most recent treatments from basic research to clinical trials, including small molecules, nucleic acids or immunotherapy, among others. It is intended to serve as a key reference for clinicians and researchers working in this field.

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“…A case series of sorafenib‐treated patients with MUM following fotemustine chemotherapy showed favourable results with reduced levels of tumour markers, partial responses and disease stabilization in three of seven patients . A more recent study also reported very similar results with this combination ; however, no objective responses or clinical improvement have been observed when sorafenib was used in combination with other standard chemotherapeutic agents, such as carboplatin and paclitaxel . Currently, phase I trials are hoping to determine the efficacy of sorafenib in combination with a different chemotherapeutic agent, lenalidomide, liver Yttrium‐90 radioembolization (NCT01893099), and also as monotherapy in a large phase II trial for patients with MUM (NCT01377025).…”

Section: Current Approaches To Systemic Therapy In Ummentioning

confidence: 97%

Evolving systemic targeted therapy strategies in uveal melanoma and implications for ophthalmic management: a review

Goh

Layton

2016

Clinical Exper Ophthalmology

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Uveal melanoma (UM) is the most common primary ocular tumour in adults. Despite good local control of the primary tumour with current methods, survival after the development of metastasis has remained poor over the last 30 years. After cutaneous melanoma, UM is the most common type of melanoma, and an ongoing debate exists regarding whether these conditions should be considered separate entities, particularly in the context of targeted therapy, where many of the initial trials for patients with metatatic cutaneous melanoma excluded metastatic UM. This paper will review the recent and ongoing investigations designed to validate systemic targeted therapy and immunotherapy in patients with metastatic UM and suggests ways in which these developments may affect management of UM by ophthalmologists in the near future.

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Response of patients with metastatic uveal melanoma to combined treatment with fotemustine and sorafenib

Cited by 12 publications

References 6 publications

Potential Onco-Suppressive Role of miR122 and miR144 in Uveal Melanoma through ADAM10 and C-Met Inhibition

Potential Onco-Suppressive Role of miR122 and miR144 in Uveal Melanoma through ADAM10 and C-Met Inhibition

Recent advances in uveal melanoma treatment

Evolving systemic targeted therapy strategies in uveal melanoma and implications for ophthalmic management: a review

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