Melanoma: Advances in Targeted Therapy and Molecular Markers

DePeralta, Danielle K.; Boland, Genevieve M.

doi:10.1245/s10434-015-4702-1

Cited by 17 publications

(12 citation statements)

References 68 publications

(65 reference statements)

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“…Melanoma is the most lethal form of skin cancer, with an enhanced ability to metastasize to distant organs via the hematogenous or lymphatic circulation ( 1 ). While recently-developed inhibitors of MAPK pathway components and immune checkpoint mediators represent the first meaningful progress in the treatment of advanced forms of melanoma ( 2 , 3 ), most patients still develop resistance to these agents and succumb to metastatic disease. Improved prognostic markers and therapeutic targets are acutely needed to optimize therapy and achieve durable responses in patients with advanced melanoma.…”

Section: Introductionmentioning

confidence: 99%

Identification of a gene expression signature associated with the metastasis suppressor function of NME1: prognostic value in human melanoma

Leonard

McCorkle

Snyder

et al. 2018

Laboratory Investigation

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SummaryWhile NME1 is well known for its ability to suppress metastasis of melanoma, the molecular mechanisms underlying this activity are not completely understood. Herein, we utilized a bioinformatics approach to systematically identify genes whose expression is correlated with the metastasis suppressor function of NME1. This was accomplished through a search for genes that were regulated by NME1, but not by NME1 variants lacking metastasis suppressor activity. This approach identified a number of novel genes, such as ALDOC, CXCL11, LRP1b and XAGE1 as well as known targets such as NETO2, which were collectively designated as an NME1-Regulated Metastasis Suppressor Signature (MSS). The MSS was associated with prolonged overall survival in a large cohort of melanoma patients in The Cancer Genome Atlas (TCGA). The median overall survival of melanoma patients with elevated expression of the MSS genes was greater than 5.6 years longer than patients with lower expression of the MSS genes. These data demonstrate that NMEl represents a powerful tool for identifying genes whose expression is associated with metastasis and survival of melanoma patients, suggesting their potential applications as prognostic markers and therapeutic targets in advanced forms of this lethal cancer.

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Section: Introductionmentioning

confidence: 99%

Identification of a gene expression signature associated with the metastasis suppressor function of NME1: prognostic value in human melanoma

Leonard

McCorkle

Snyder

et al. 2018

Laboratory Investigation

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“…In the recent years, mutations of B-RAF , especially the V600E, have been reported in different types of cancer ( Davies et al, 2002 ): in the 50% of melanomas ( DePeralta and Boland, 2015 ; El-Gamal et al, 2016 ) and papillary thyroid carcinomas ( Jiang et al, 2016 ), in about 10% of colon ( Tie and Desai, 2015 ) and ovarian cancers ( Pakneshan et al, 2013 ), and in rare cases (1-3%) of non-small cell lung cancer ( Caparica et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

The Droplet Digital PCR: A New Valid Molecular Approach for the Assessment of B-RAF V600E Mutation in Hairy Cell Leukemia

et al. 2016

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Hairy cell leukemia (HCL) is a chronic lymphoproliferative B-cell disorder where the B-RAF V600E mutation has been recently detected, as reported for solid neoplasias but not for other B-cell lymphomas. The digital droplet PCR (dd-PCR) is a molecular technique that, without standard references, is able to accurately quantitate DNA mutations. ddPCR could be an useful instrument for the detection of the B-RAF V600E mutation in HCL, where the minimal residual disease monitoring is fundamental for planning a patients-targeted treatment in the era of new anti-CD20 and anti-RAF compounds. This retrospective study enrolled 47 patients observed at the Hematology Unit of the University of Pisa, Italy, from January 2005 to January 2014: 27 patients were affected by “classic” HCL, two by the variant HCL (vHCL), and 18 by splenic marginal zone lymphoma (SMZL). The aim of the study was to compare dd-PCR to “classic” quantitative PCR (QT-PCR) in terms of sensitivity and specificity and to demonstrate its possible use in HCL. Results showed that: (1) the sensitivity of dd-PCR is about half a logarithm superior to QT-PCR (5 × 10-5 vs. 2.5 × 10-4), (2) the specificity of the dd-PCR is comparable to QT-PCR (no patient with marginal splenic lymphoma or HCL variant resulted mutated), (3) its high sensitivity would allow to use dd-PCR in the monitoring of MRD. At the end of treatment, among patients in complete remission, 33% were still MRD-positive by dd-PCR versus 28% by QT-PCR versus 11% by the evaluation of the B-cell clonality, after 12 months, dd-PCR was comparable to QT-PCR and both detected the B-RAF mutation in 15% of cases defined as MRD-negative by IgH rearrangement. Moreover, (4) the feasibility and the costs of dd-PCR are comparable to those of QT-PCR. In conclusion, our study supports the introduction of dd-PCR in the scenario of HCL, also during the follow-up.

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“…By 2030, the number of newly diagnosed cases is expected to more than double, while the annual cost of treating newly diagnosed melanomas is estimated to triple (13). Melanoma treatment costs may increase even faster than expected given new targeted therapies and immunotherapies that have been approved in recent years (14). …”

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confidence: 99%