<i>NRAS</i>
            Mutant Melanoma: An Overview for the Clinician for Melanoma Management

Jenkins, Russell W.; Sullivan, Ryan J.

doi:10.2217/mmt.15.40

Cited by 14 publications

(11 citation statements)

References 125 publications

(124 reference statements)

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“…Reliable diagnostic markers and the assessment of the molecular status of the tumor in the patients are required for an effective targeted therapy in the treatment of high TMB melanoma, leading to an approved adjuvant therapy that can be used among patients with advanced MM 11 , 12 , 20 . To the best of our best knowledge, we are the first showing that current serological and immunohistochemical markers in melanoma had significantly limited the detection of the advanced stage of this disease, which metastasized from the primary site 35 – 37 .…”

Section: Discussionmentioning

confidence: 99%

“…Melanoma patients with a defined TMB and carrying mutations in the cancer genome can benefit from early diagnosis 13 – 15 . An effective diagnostic strategy to identify BRAF/NRAS MM can allow the development of a subsequent targeted therapy that can improve the prognostic outcomes and therapeutic approaches among advanced MM patients 11 , 16 – 19 . The intra-tumoral heterogeneity of these genes leads to changes in the diagnostic and therapeutic strategies of melanoma, and personalized treatments and targeted therapies against melanoma have emerged 15 , 20 .…”

Section: Introductionmentioning

confidence: 99%

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PLA1A expression as a diagnostic marker of BRAF-mutant metastasis in melanoma cancer

Liu

Maghsoudloo

et al. 2021

Sci Rep

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BRAF and NRAS are the most reported mutations associated to melanomagenesis. The lack of accurate diagnostic markers in response to therapeutic treatment in BRAF/NRAS-driven melanomagenesis is one of the main challenges in melanoma personalized therapy. In order to assess the diagnostic value of phosphatidylserine-specific phospholipase A1-alpha (PLA1A), a potent lysophospholipid mediating the production of lysophosphatidylserine, PLA1A mRNA and serum levels were compared in subjects with malignant melanoma (n = 18), primary melanoma (n = 13), and healthy subjects (n = 10). Additionally, the correlation between histopathological subtypes of BRAF/NRAS-mutated melanoma and PLA1A was analyzed. PLA1A expression was significantly increased during melanogenesis and positively correlated to disease severity and histopathological markers of metastatic melanoma. PLA1A mRNA and serum levels were significantly higher in patients with BRAF-mutated melanoma compared to the patients with NRAS-mutated melanoma. Notably, PLA1A can be used as a diagnostic marker for an efficient discrimination between naïve melanoma samples and advanced melanoma samples (sensitivity 91%, specificity 57%, and AUC 0.99), as well as BRAF-mutated melanoma samples (sensitivity 62%, specificity 61%, and AUC 0.75). Our findings suggest that PLA1A can be considered as a potential diagnostic marker for advanced and BRAF-mutated melanoma.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

PLA1A expression as a diagnostic marker of BRAF-mutant metastasis in melanoma cancer

Liu

Maghsoudloo

et al. 2021

Sci Rep

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“…ROS not only trigger the occurrence and development of melanoma by way of genotoxicity and some specific signaling pathway activation but they also cause oncogene activation or tumor-suppressing gene inactivation in melanoma consisting of BRAF, c-Myc, p53, and Ras genes. N-Ras is upstream of the MAPK pathway, and its mutation commonly occurs in melanoma, which contributes to cancer cell proliferation [65]. Moreover, ROS also drive the stable expression of HIF-1 α to activate the Met protooncogene, which facilitates the proliferation of the extracellular matrix, angiogenesis, and the proliferation and metastasis of melanoma cells [66].…”

Section: Relationship Between Ros and Skin Cancermentioning

confidence: 99%

Emerging Perspective: Role of Increased ROS and Redox Imbalance in Skin Carcinogenesis

Xian

Lai

Song

et al. 2019

Oxidative Medicine and Cellular Longevity

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Strategies to battle malignant tumors have always been a dynamic research endeavour. Although various vehicles (e.g., chemotherapeutic therapy, radiotherapy, surgical resection, etc.) are used for skin cancer management, they mostly remain unsatisfactory due to the complex mechanism of carcinogenesis. Increasing evidence indicates that redox imbalance and aberrant reactive oxygen species (ROS) are closely implicated in the oncogenesis of skin cancer. When ROS production goes beyond their clearance, excessive or accumulated ROS could disrupt redox balance, induce oxidative stress, and activate the altered ROS signals. These would damage cellular DNA, proteins, and lipids, further leading to gene mutation, cell hyperproliferation, and fatal lesions in cells that contribute to carcinogenesis in the skin. It has been known that ROS-mediated skin carcinogenesis involves multiple ways, including modulating related signaling pathways, changing cell metabolism, and causing the instability of the genome and epigenome. Nevertheless, the exact role of ROS in skin cancer has not been thoroughly elucidated. In spite of ROS inducing skin carcinogenesis, toxic-dose ROS could trigger cell death/apoptosis and, therefore, may be an efficient therapeutic tool to battle skin cancer. Considering the dual role of ROS in the carcinogenesis and treatment of skin cancer, it would be essential to clarify the relationship between ROS and skin cancer. Thus, in this review, we get the related data together to seek the connection between ROS and skin carcinogenesis. Besides, strategies basing on ROS to fight skin cancer are discussed.

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“…The most frequent K-Ras mutations are in residues Gly12, Gly13 and Gln61 (Hobbs et al, 2016;Li et al, 2018). N-Ras is mutated in about 20% of all melanoma patients (Jenkins and Sullivan, 2016). H-Ras mutations are comparatively rare (Prior et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Developing Small Molecules that Inhibit K-Ras/GTP Binding Based on New Affinity Measurements

Carta¹,

Hutcheson²,

Davis

et al. 2020

Preprint

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SUMMARYRAS genes encode small GTPases essential for proliferation, differentiation, and survival of mammalian cells. RAS gene mutations are associated with approximately 30% of all human cancers. However, based on measurements reported three decades ago of Ras protein affinities to GTP in the 10-20 picomolar range, it has been accepted in the scientific and medical communities that Ras proteins are undruggable targets. Here, we report MicroScale Thermophoresis and scintillation proximity assay measurements of the affinity of K-Ras and several K-Ras mutants for GTP in the range of 200 nanomolar, a 10,000-fold difference from that previously reported, and the identification of over 400 small molecules that block GTP binding to K-Ras. Focusing on two of those molecules, we report small molecule inhibition of Ras downstream signaling and cellular proliferation in human pancreatic and non-small cell lung cancer cells expressing wild type and K-Ras G12C, G12D and G12S, and N-Ras Q61K mutants.

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NRAS Mutant Melanoma: An Overview for the Clinician for Melanoma Management

Cited by 14 publications

References 125 publications

PLA1A expression as a diagnostic marker of BRAF-mutant metastasis in melanoma cancer

PLA1A expression as a diagnostic marker of BRAF-mutant metastasis in melanoma cancer

Emerging Perspective: Role of Increased ROS and Redox Imbalance in Skin Carcinogenesis

Developing Small Molecules that Inhibit K-Ras/GTP Binding Based on New Affinity Measurements

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