How breakthroughs in translational research have impacted treatment strategies for melanoma

Verykiou, Stamatina; Edwards, Noel; Hill, David S.

doi:10.1111/bjd.16112

Cited by 3 publications

(3 citation statements)

References 23 publications

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“…CM spread has been proven in numerous studies to be the result of genetic mutations and alterations in the microenvironment, mainly the overexpression of proteins that assist in tumor infiltration. CM progression is supposed to derive from the proliferation of cellular subpopulations that also acquire stem‐like characteristics in response to elements including the microenvironment; the role of driver mutations in melanoma oncogenicity may be tissue‐dependent.…”

Section: Introductionmentioning

confidence: 99%

Melanoma types by in vivo reflectance confocal microscopy correlated with protein and molecular genetic alterations: A pilot study

Beretti

Bertoni

Farnetani

et al. 2019

Experimental Dermatology

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Cutaneous melanoma (CM) is one of the most prevalent skin cancers, which lacks both a prognostic marker and a specific and lasting treatment, due to the complexity of the disease and heterogeneity of patients. Reflectance confocal microscopy (RCM) in vivo analysis is a versatile approach offering immediate morphological information, enabling the identification of four primary cutaneous RCM CM types. Whether RCM CM types are associated with a specific protein and molecular genetic profiles at the tissue level remains unclear. The current pilot study was designed to identify potential correlations between RCM CM types and specific biological characteristics, combining immunohistochemistry (IHC) and molecular analyses. Eighty primary CMs evaluated at patient bedside with RCM (type 1 [19, 24%], type 2 [12, 15%], type 3 [7, 9%] and type 4 [42, 52%]) were retrospectively evaluated by IHC stains (CD271, CD20, CD31, cyclin D1), fluorescence in situ hybridization FISH for MYC gain and CDKN2A loss and molecular analysis for somatic mutations (BRAF, NRAS and KIT). RCM CM types correlated with markers of stemness property, density of intra‐tumoral lymphocytic B infiltrate and cyclin D1 expression, while no significant association was found with blood vessel density nor molecular findings. RCM CM types show a different marker profile expression, suggestive of a progression and an increase in aggressiveness, according to RCM morphologies.

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Section: Introductionmentioning

confidence: 99%

Melanoma types by in vivo reflectance confocal microscopy correlated with protein and molecular genetic alterations: A pilot study

Beretti

Bertoni

Farnetani

et al. 2019

Experimental Dermatology

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“…This mutation activates the downstream effector mitogen-activated protein kinase kinase (MEK). Therefore, selective BRAF and MEK inhibitors (BRAFi/MEKi) have been introduced [ 4 , 5 , 6 ], but patients often relapse after treatment due to the development of drug resistance.…”

Section: Introductionmentioning

confidence: 99%

Reactive Oxygen Species Regulation of Chemoresistance and Metastatic Capacity of Melanoma: Role of the Cancer Stem Cell Marker CD271

et al. 2023

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BRAF mutations are present in 30–50% of cases of cutaneous melanoma, and treatment with selective BRAF and MEK inhibitors has been introduced. However, the development of resistance to these drugs often occurs. Chemo-resistant melanoma cells show increased expression of CD271, a stem cell marker that features increased migration. Concordantly, resistance to the selective inhibitor of oncogenic BRAFV600E/K, vemurafenib, is mediated by the increased expression of CD271. It has recently been shown that the BRAF pathway leads to an overexpression of the NADPH oxidase Nox4, which produces reactive oxygen species (ROS). Here, we examined in vitro how Nox-derived ROS in BRAF-mutated melanoma cells regulates their drug sensitivity and metastatic potential. We demonstrated that DPI, a Nox inhibitor, reduced the resistance of a melanoma cell line (SK-MEL-28) and a primary culture derived from a BRAFV600E-mutated biopsy to vemurafenib. DPI treatment affected the expression of CD271 and the ERK and Akt signaling pathways, leading to a drop in epithelial–mesenchymal transition (EMT), which undoubtedly promotes an invasive phenotype in melanoma. More importantly, the scratch test demonstrated the efficacy of the Nox inhibitor (DPI) in blocking migration, supporting its use to counteract drug resistance and thus cell invasion and metastasis in BRAF-mutated melanoma.

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“…activate the downstream effector mitogen‐activated protein kinase kinase (MEK) to drive melanoma tumour growth. Despite improvements in clinical outcome since the introduction of selective BRAF and MEK inhibitors (BRAFi/MEKi) and immune checkpoint inhibitors, development of resistance to these drugs remains a major problem, with little improvement in overall patient survival . Proposed mechanisms of resistance to BRAFi/MEKi treatment include selection of melanoma subpopulations with inherent genetic/epigenetic changes, or the induction of generic stress‐induced response mechanisms that raise the survival threshold of the cell .…”

mentioning

confidence: 99%

Harnessing autophagy to overcome mitogen‐activated protein kinase kinase inhibitor‐induced resistance in metastatic melanoma

et al. 2018

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How breakthroughs in translational research have impacted treatment strategies for melanoma

Cited by 3 publications

References 23 publications

Melanoma types by in vivo reflectance confocal microscopy correlated with protein and molecular genetic alterations: A pilot study

Melanoma types by in vivo reflectance confocal microscopy correlated with protein and molecular genetic alterations: A pilot study

Reactive Oxygen Species Regulation of Chemoresistance and Metastatic Capacity of Melanoma: Role of the Cancer Stem Cell Marker CD271

Harnessing autophagy to overcome mitogen‐activated protein kinase kinase inhibitor‐induced resistance in metastatic melanoma

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