A twenty year perspective on melanoma therapy

Flaherty, Keith T.

doi:10.1111/pcmr.13125

Cited by 3 publications

(11 citation statements)

References 142 publications

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“…This pathway, which includes RAS, RAF, ERK, and mitogen-activated extracellular signal-regulated kinase (MEK), is crucial for regulating cellular proliferation [ 2 ]. The discovery of activating NRAS mutations in melanoma in the mid-1980s and the subsequent identification of BRAF mutations in 2002 have been significant milestones in understanding melanoma’s molecular pathology [ 12 ]. Both of these mutations lead to the overactivation of the MAPK/ERK pathway, promoting melanoma cell proliferation and survival.…”

Section: Molecular Pathology Of Melanomamentioning

confidence: 99%

“…The exploration of the MAP kinase pathway as a therapeutic target began with responses observed from MEK inhibitors. However, the development of potent and selective inhibitors such as vemurafenib, dabrafenib, and encorafenib, which target mutated BRAF, has been the major breakthrough in melanoma treatment [ 12 ]. The late 2000s saw a pivotal shift with the introduction of these targeted therapies.…”

Section: Molecular Pathology Of Melanomamentioning

confidence: 99%

“…The late 2000s saw a pivotal shift with the introduction of these targeted therapies. The initial use of drugs such as sorafenib paved the way for more effective and selective BRAF inhibitors [ 12 ].…”

Section: Molecular Pathology Of Melanomamentioning

confidence: 99%

“…Combination therapies of BRAF/MEK inhibitors have significantly improved the efficacy of melanoma treatments, with reduced toxicity and longer progression-free survival (PFS) times compared with monotherapies [ 12 ]. These advances highlight the significance of the MAPK/ERK pathway in melanoma’s molecular pathology and response to therapy, underscoring the importance of understanding the influence of these mutations when developing effective treatments.…”

Section: Molecular Pathology Of Melanomamentioning

confidence: 99%

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Molecular Frontiers in Melanoma: Pathogenesis, Diagnosis, and Therapeutic Advances

Kim,

Kim

2024

IJMS

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Melanoma, a highly aggressive skin cancer, is characterized by rapid progression and high mortality. Recent advances in molecular pathogenesis have shed light on genetic and epigenetic changes that drive melanoma development. This review provides an overview of these developments, focusing on molecular mechanisms in melanoma genesis. It highlights how mutations, particularly in the BRAF, NRAS, c-KIT, and GNAQ/GNA11 genes, affect critical signaling pathways. The evolution of diagnostic techniques, such as genomics, transcriptomics, liquid biopsies, and molecular biomarkers for early detection and prognosis, is also discussed. The therapeutic landscape has transformed with targeted therapies and immunotherapies, improving patient outcomes. This paper examines the efficacy, challenges, and prospects of these treatments, including recent clinical trials and emerging strategies. The potential of novel treatment strategies, including neoantigen vaccines, adoptive cell transfer, microbiome interactions, and nanoparticle-based combination therapy, is explored. These advances emphasize the challenges of therapy resistance and the importance of personalized medicine. This review underlines the necessity for evidence-based therapy selection in managing the increasing global incidence of melanoma.

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Section: Molecular Pathology Of Melanomamentioning

confidence: 99%

Section: Molecular Pathology Of Melanomamentioning

confidence: 99%

Section: Molecular Pathology Of Melanomamentioning

confidence: 99%

Section: Molecular Pathology Of Melanomamentioning

confidence: 99%

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Molecular Frontiers in Melanoma: Pathogenesis, Diagnosis, and Therapeutic Advances

Kim,

Kim

2024

IJMS

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“…The melanogenic activity and behavior of melanocytes are regulated by numerous factors, such as ultraviolet radiation (UVR) and chemical and biological mediators encompassing hormonal and non-hormonal regulators, as well as genetic and molecular ones [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ]. The most prevalent types of melanomas include cutaneous malignant melanomas which affect large segments of the population with high incidence and mortality rates compared to other cancers [ 2 , 6 , 11 , 15 , 16 , 17 , 18 , 19 ]. However, melanomas also originate from melanocytes of the eye and mucosa (including oral, anorectal, and genitourinary melanomas) with very rare melanomas arising from other organs including the central nervous system (CNS) [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ].…”

Section: Introductionmentioning

confidence: 99%

Malignant Melanoma: An Overview, New Perspectives, and Vitamin D Signaling

Slominski,

Kim,

Janjetovic

et al. 2024

Cancers

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Melanoma, originating through malignant transformation of melanin-producing melanocytes, is a formidable malignancy, characterized by local invasiveness, recurrence, early metastasis, resistance to therapy, and a high mortality rate. This review discusses etiologic and risk factors for melanoma, diagnostic and prognostic tools, including recent advances in molecular biology, omics, and bioinformatics, and provides an overview of its therapy. Since the incidence of melanoma is rising and mortality remains unacceptably high, we discuss its inherent properties, including melanogenesis, that make this disease resilient to treatment and propose to use AI to solve the above complex and multidimensional problems. We provide an overview on vitamin D and its anticancerogenic properties, and report recent advances in this field that can provide solutions for the prevention and/or therapy of melanoma. Experimental papers and clinicopathological studies on the role of vitamin D status and signaling pathways initiated by its active metabolites in melanoma prognosis and therapy are reviewed. We conclude that vitamin D signaling, defined by specific nuclear receptors and selective activation by specific vitamin D hydroxyderivatives, can provide a benefit for new or existing therapeutic approaches. We propose to target vitamin D signaling with the use of computational biology and AI tools to provide a solution to the melanoma problem.

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Thin Amelanotic and Hypomelanotic Melanoma: Clinicopathological and Dermoscopic Features

Paolino,

Pampena,

Di Ciaccio

et al. 2024

Medicina

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Background and Objectives: Amelanotic/hypomelanotic melanomas (AHMs) account for 2–8% of all cutaneous melanomas. Due to their clinical appearance and the lack of specific dermoscopic indicators, AHMs are challenging to diagnose, particularly in thinner cutaneous lesions. The aim of our study was to evaluate the clinicopathological and dermoscopic features of thin AHMs. Identifying the baseline clinical–pathological features and dermoscopic aspects of thin AHMs is crucial to better understand this entity. Materials and Methods: We divided the AHM cohort into two groups based on Breslow thickness: thin (≤1.00 mm) and thick (>1.00 mm). This stratification helped identify any significant clinicopathological differences between the groups. For dermoscopic analysis, we employed the “pattern analysis” approach, which involves a simultaneous and subjective assessment of different criteria. Results: Out of the 2.800 melanomas analyzed for Breslow thickness, 153 were identified as AHMs. Among these, 65 patients presented with thin AHMs and 88 with thick AHMs. Red hair color and phototype II were more prevalent in patients with thin AHMs. The trunk was the most common anatomic site for thin AHMs. Patients with thin AHMs showed a higher number of multiple melanomas. Dermoscopic analysis revealed no significant difference between thin AHMs and thick AHMs, except for a more frequent occurrence of residual reticulum in thin AHMs. Conclusions: Thin AHMs typically affect individuals with lower phototypes and red hair color. These aspects can be related to the higher presence of pheomelanin, which provides limited protection against sun damage. This also correlates with the fact that the trunk, a site commonly exposed to intermittent sun exposure, is the primary anatomical location for thin AHMs. Multiple primary melanomas are more common in patients with thin AHMs, likely due to an intrinsic predisposition as well as greater periodic dermatologic follow-ups in this class of patients. Apart from the presence of residual reticulum, no other significant dermoscopic differences were observed, complicating the differential diagnosis between thin and thick AHMs based on dermoscopy alone.

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A twenty year perspective on melanoma therapy

Cited by 3 publications

References 142 publications

Molecular Frontiers in Melanoma: Pathogenesis, Diagnosis, and Therapeutic Advances

Molecular Frontiers in Melanoma: Pathogenesis, Diagnosis, and Therapeutic Advances

Malignant Melanoma: An Overview, New Perspectives, and Vitamin D Signaling

Thin Amelanotic and Hypomelanotic Melanoma: Clinicopathological and Dermoscopic Features

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