Molecular genetic and immunotherapeutic targets in metastatic melanoma

Melis, C.; Rogiers, Aljosja; Bechter, Oliver

doi:10.1007/s00428-017-2113-3

Cited by 20 publications

(28 citation statements)

References 85 publications

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“…15,16 However, most patients develop resistance to BRAF-targeted therapies after a short period of time. 17 Thus, longitudinal monitoring of these patients is crucial for disease outcome. Levels of BRAF V600E in cfDNA (cfBRAF V600E ) correlate with tumour burden, treatment response and disease progression in patients with metastatic BRAF V600E melanoma.…”

Section: Discussionmentioning

confidence: 99%

“…Stratification of patients with metastatic melanoma based on BRAF mutation status is crucial for treatment selection, as BRAF V600E inhibitors improve the progression‐free and overall survival rates in patients with metastatic BRAF V600E melanoma . However, most patients develop resistance to BRAF‐targeted therapies after a short period of time . Thus, longitudinal monitoring of these patients is crucial for disease outcome.…”

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confidence: 99%

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Detection of cell‐free circulating BRAF ^V ^600E by droplet digital polymerase chain reaction in patients with and without melanoma under dermatological surveillance

et al. 2019

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Summary Background The p.V600E mutation in the BRAF protein is the most frequent mutation in cutaneous melanoma and is a recurrent alteration found in common benign naevi. Analysis of the cell‐free BRAF c.1799T>A, p.V600E mutation (cfBRAFV600E) in plasma has emerged as a biomarker for monitoring prognosis and treatment response in patients with melanoma. Objectives To quantify cfBRAFV600E levels in plasma from patients with melanoma and from patients without melanoma undergoing regular follow‐up of their melanocytic lesions, in order to assess the clinical significance of the test. Methods We quantified cfBRAFV600E by droplet digital polymerase chain reaction in plasma from 146 patients without melanoma undergoing continuous dermatological screening, from 26 stage III and seven stage IV patients with BRAF‐mutant melanoma, and from 32 patients with melanoma who were free of disease for 3 or more years. Results Among disease‐free patients and individuals without melanoma, 52% presented a high naevus count (> 50) and 49% had clinically atypical naevi. cfBRAFV600E was detected in 71% of patients with stage IV melanoma and 15% with stage III, and in 1·4% of individuals without melanoma. No cfBRAFV600E mutation was detected in disease‐free patients with melanoma. Individuals without melanoma had lower cfBRAFV600E levels than patients with melanoma. We established a variant allelic frequency of 0·26% or 5 copies mL−1 of cfBRAFV600E as the optimal cutoff value for identifying patients with melanoma with > 99% specificity. Conclusions This study suggests that naevus‐related factors do not influence the detection of cfBRAFV600E in individuals without melanoma, and supports the clinical diagnostic value of plasma cfBRAFV600E quantification in patients with melanoma. What's already known about this topic? The analysis of the BRAF c.1799T>A (p.V600E) mutation in cell‐free (cf)DNA has emerged as a potential biomarker for monitoring prognosis and treatment response in patients with metastatic BRAFV600E melanoma. The BRAFV600E alteration is a common genetic alteration found in benign proliferations such as melanocytic naevi. No information exists about the impact of the number of common acquired naevi or the presence of clinically atypical naevi in cfBRAFV600E detection in an individual. What does this study add? The cfBRAFV600E mutation is detected in plasma from a reduced number of individuals without melanoma undergoing continuous dermatological follow‐up. A high number of naevi or the presence of clinically atypical naevi are factors that do not influence cfBRAFV600E detection in an individual. Both total cfBRAF concentration and cfBRAFV600E frequency are effective biomarkers in patients with advanced melanoma but not in patients at early stages or with micrometastases. What is the translational message? Detection of cfBRAFV600E in an individual is not influenced by naevus‐related factors. cfBRAFV600E is a robust and reliable biomarker that can be used in dermatological surveillance programmes.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Detection of cell‐free circulating BRAF ^V ^600E by droplet digital polymerase chain reaction in patients with and without melanoma under dermatological surveillance

et al. 2019

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“…However, this seems to be strongly dependent on the cancer entity, as in case of advanced prostate cancer no comparable observations have been described . Melanoma is a cancer with high mutation frequency, and this might well be responsible for the fact that stronger immune responses can be triggered in melanoma than in other cancer entities . A clinical observation which underlines this increased anti‐melanoma activity is the development of vitiligo upon, e.g.…”

Section: Observations In Different Cancer Entitiesmentioning

confidence: 99%

“…167 Melanoma is a cancer with high mutation frequency, and this might well be responsible for the fact that stronger immune responses can be triggered in melanoma than in other cancer entities. 168,169 A clinical observation which underlines this increased anti-melanoma activity is the development of vitiligo upon, e.g. Pembrolizumab treatment.…”

Section: Melanomamentioning

confidence: 99%

Abscopal, immunological effects of radiotherapy: Narrowing the gap between clinical and preclinical experiences

Brix

Tiefenthaller

Anders

et al. 2017

Immunological Reviews

166

156

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SummaryRadiotherapy-despite being a local therapy that meanwhile is characterized by an impressively high degree of spatial accuracy-can stimulate systemic phenomena which occasionally lead to regression and rejection of non-irradiated, distant tumor lesions. These abscopal effects of local irradiation have been observed in sporadic clinical case reports since the beginning of the 20th century, and extensive preclinical work has contributed to identify systemic anti-tumor immune responses as the underlying driving forces. Although abscopal tumor regression still remains a rare event in the radiotherapeutic routine, increasing numbers of cases are being reported, particularly since the clinical implementation of immune checkpoint inhibiting agents. Accordingly, interests to systematically exploit the therapeutic potential of radiotherapy-stimulated systemic responses are constantly growing. The present review briefly delineates the history of radiotherapy-induced abscopal effects and the activation of systemic anti-tumor immune responses by local irradiation. We discuss preclinical and clinical reports with specific focus on the corresponding controversies, and we propose issues that should be addressed in the future in order to narrow the gap between preclinical knowledge and clinical experiences. K E Y W O R D Sabscopal effect, anti-tumor immunity, immunogenic cell death, radiotherapy | INTRODUCTIONTogether with surgery and chemotherapy, radiotherapy (RT) plays a central role in oncological treatment regimens. More than 60% of all cancer patients receive RT at one point during their medical attendance. 1 Traditionally, the efficacy of RT has been exclusively credited to its ability to induce cancer cell death and the notion that tumors are more prone to damage induced by ionizing radiation (IR) than non-malignant, normal tissues. According to the concept of the four R's of radiotherapy, repair (of IR-induced damage), reoxygenation, redistribution (to other cell cycle phases), and regeneration are the major determinants of a tissue's response toward IR.2 Importantly, tumors and non-malignant tissues are considered to differ in these characteristics, thus forming the rationale for the use of fractionated irradiation regimens with daily fractions over a period of 3-6 weeks in the clinical routine.It needs to be stressed that in the majority of all cases RT is applied in local settings with a high degree of spatial precision and the cardinal aim to achieve locoregional tumor control. However, there is accumulating evidence that-although applied locally-RT can induce systemic anti-tumor responses leading to regression and rejection of non-irradiated, distant tumor lesions. Collectively, these observations have been summarized under the term 'abscopal effects of RT', and meanwhile it is well accepted that immune mechanisms are the underlying driving forces. For distinct chemotherapeutics, the induction of such systemic, immune-mediated effects has been extensively analyzed by the groups of G. Kroemer and L. ZitvogeI....

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“…Similar to other miRNAs, they target particular genes, namely PTEN, a moderator gene of PI3K signaling pathway (25,26). Multiple miRNAs, including miR-199a-5p and miR-1908, comprise the oncomiR group.…”

Section: Oncomirsmentioning

confidence: 99%

Melanoma and Associated MicroRNAs

2016

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Context: Melanoma is an invasive type of skin cancer, with a rapidly increasing incidence. Therefore, new approaches are required to treat this aggressive cancer. MicroRNAs (miRNAs) are introduced as novel components in melanoma. This review study aimed to determine the relationship between melanoma and miRNAs. Evidence Acquisition: Prognostic, diagnostic, and therapeutic applications of miRNAs in skin cancer have been recently investigated from different aspects. Some of these studies on miRNAs were reviewed, and the mechanisms of some genetic modifications were determined in this study. Results: Since recommendations for miRNAs have increased in the past decades, and scientists have confirmed their great efficacy in multiple aspects of cancer treatment, different strategies have been developed considering their therapeutic effects. Therefore, further studies are required to confirm miRNA application in melanoma treatment. Conclusions: This review study included various investigations concerning miRNA traces as molecular rearrangements in melanoma. It was revealed that multiple miRNAs are efficient in molecular signaling and can be used as prognostic, diagnostic, and therapeutic biomarkers. Although the exact relationship between aberrant expression of miRNAs and cancers has been confirmed, further studies are required to introduce more thorough and accurate applications of miRNAs in melanoma.

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Molecular genetic and immunotherapeutic targets in metastatic melanoma

Cited by 20 publications

References 85 publications

Detection of cell‐free circulating BRAF ^V ^600E by droplet digital polymerase chain reaction in patients with and without melanoma under dermatological surveillance

Detection of cell‐free circulating BRAF ^V ^600E by droplet digital polymerase chain reaction in patients with and without melanoma under dermatological surveillance

Abscopal, immunological effects of radiotherapy: Narrowing the gap between clinical and preclinical experiences

Melanoma and Associated MicroRNAs

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Molecular genetic and immunotherapeutic targets in metastatic melanoma

Cited by 20 publications

References 85 publications

Detection of cell‐free circulating BRAF V 600E by droplet digital polymerase chain reaction in patients with and without melanoma under dermatological surveillance

Detection of cell‐free circulating BRAF V 600E by droplet digital polymerase chain reaction in patients with and without melanoma under dermatological surveillance

Abscopal, immunological effects of radiotherapy: Narrowing the gap between clinical and preclinical experiences

Melanoma and Associated MicroRNAs

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Product

Resources

About

Detection of cell‐free circulating BRAF ^V ^600E by droplet digital polymerase chain reaction in patients with and without melanoma under dermatological surveillance

Detection of cell‐free circulating BRAF ^V ^600E by droplet digital polymerase chain reaction in patients with and without melanoma under dermatological surveillance