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Journal of Cellular Physiology Jan 2010Melanocytes are pigment-producing cells in the skin of humans and other vertebrates. A number of genes involved in melanocyte development and vertebrate pigmentation... (Review)
Review
Melanocytes are pigment-producing cells in the skin of humans and other vertebrates. A number of genes involved in melanocyte development and vertebrate pigmentation have been characterized, largely through studies of a diversity of pigment mutations in a variety of species. Embryonic development of the melanocyte initiates with cell fate specification in the neural crest, which is then followed by cell migration and niche localization. Many genes involved in melanocyte development have also been implicated in the development of melanoma, an aggressive and fatal form of skin cancer that originates in the melanocyte. Although early stage melanomas that have not spread to the lymph nodes can be excised with little risk of recurrence, patients diagnosed with metastatic melanoma have a high mortality rate due to the resistance of most tumors to radiotherapy and chemotherapy. Transformed melanocytes that develop into melanomas proliferate abnormally and often begin to grow radially in the skin. Vertical growth can then follow this radial growth, leading to an invasion through the basement membrane into the underlying dermis and subsequent metastasis. It is still unclear, however, how a normal melanocyte becomes a melanoma cell, and how melanoma utilizes the properties of the normal melanocyte and its progenitors in its progression. The goal of this mini-review is to highlight the role of melanocyte developmental pathways in melanoma, and to discuss recent studies and tools being used to illuminate this connection.
Topics: Animals; Embryonic Development; Humans; Melanocytes; Melanoma; Signal Transduction
PubMed: 19795394
DOI: 10.1002/jcp.21935 -
Oncology (Williston Park, N.Y.) Jul 2009Melanoma, a cancer of melanocytes, pigment-producing cells in the skin, is the most serious form of skin cancer. Its incidence is increasing rapidly and reaching... (Review)
Review
Melanoma, a cancer of melanocytes, pigment-producing cells in the skin, is the most serious form of skin cancer. Its incidence is increasing rapidly and reaching epidemic proportions. When detected early, it is considered curable, but when detected at later stages it is arguably one of the most lethal malignancies and is the cause of more years of lost life than any other cancer except leukemia. Because most cutaneous melanomas are visible, however, melanoma in general is a cancer highly amenable to early detection. Surgery is standard treatment for localized melanoma. There is no standard therapy for advanced-stage melanoma. Metastatic melanoma disseminates widely and it frequently involves sites that are not commonly affected in other cancers, such as the gastrointestinal tract and skin. The median survival time for patients with metastatic melanoma is less than 1 year. Despite these grim statistics, long-term survival occurs occasionally. This article will review diagnosis, staging, and treatment for malignant melanoma and will discuss the nursing role in the care of patients with melanoma.
Topics: Antineoplastic Agents; Combined Modality Therapy; Early Detection of Cancer; Humans; Immunotherapy; Lymph Node Excision; Melanoma; Neoplasm Staging; Nurse's Role; Nursing Assessment; Oncology Nursing; Patient Education as Topic; Physical Examination; Prognosis; Risk Factors; Skin Neoplasms; United States
PubMed: 19860037
DOI: No ID Found -
JAMA Dermatology Dec 2021Early melanoma diagnosis is associated with better health outcomes, but there is insufficient evidence that screening, such as having routine skin checks, reduces...
IMPORTANCE
Early melanoma diagnosis is associated with better health outcomes, but there is insufficient evidence that screening, such as having routine skin checks, reduces mortality.
OBJECTIVE
To assess melanoma-specific and all-cause mortality associated with melanomas detected through routine skin checks, incidentally or patient detected. A secondary aim was to examine patient, sociodemographic, and clinicopathologic factors associated with different modes of melanoma detection.
DESIGN, SETTING, AND PARTICIPANTS
This prospective, population-based, cohort study included patients in New South Wales, Australia, who were diagnosed with melanoma over 1 year from October 23, 2006, to October 22, 2007, in the Melanoma Patterns of Care Study and followed up until 2018 (mean [SD] length of follow-up, 11.9 [0.3] years) by using linked mortality and cancer registry data. All patients who had invasive melanomas recorded at the cancer registry were eligible for the study, but the number of in situ melanomas was capped. The treating doctors recorded details of melanoma detection and patient and clinical characteristics in a baseline questionnaire. Histopathologic variables were obtained from pathology reports. Of 3932 recorded melanomas, data were available and analyzed for 2452 (62%; 1 per patient) with primary in situ (n = 291) or invasive (n = 2161) cutaneous melanoma. Data were analyzed from March 2020 to January 2021.
MAIN OUTCOMES AND MEASURES
Melanoma-specific mortality and all-cause mortality.
RESULTS
A total of 2452 patients were included in the analyses. The median age at diagnosis was 65 years (range, 16-98 years), and 1502 patients (61%) were men. A total of 858 patients (35%) had their melanoma detected during a routine skin check, 1148 (47%) self-detected their melanoma, 293 (12%) had their melanoma discovered incidentally when checking another skin lesion, and 153 (6%) reported "other" presentation. Routine skin-check detection of invasive melanomas was associated with 59% lower melanoma-specific mortality (subhazard ratio, 0.41; 95% CI, 0.28-0.60; P < .001) and 36% lower all-cause mortality (hazard ratio, 0.64; 95% CI, 0.54-0.76; P < .001), adjusted for age and sex, compared with patient-detected melanomas. After adjusting for prognostic factors including ulceration and mitotic rate, the associations were 0.68 (95% CI, 0.44-1.03; P = .13), and 0.75 (95% CI, 0.63-0.90; P = .006), respectively. Factors associated with higher odds of routine skin-check melanoma detection included being male (female vs male, odds ratio [OR], 0.73; 95% CI, 0.60-0.89; P = .003), having previous melanoma (vs none, OR, 2.36; 95% CI, 1.77-3.15; P < .001), having many moles (vs not, OR, 1.39; 95% CI, 1.10-1.77; P = .02), being 50 years or older (eg, 50-59 years vs <40 years, OR, 2.89; 95% CI, 1.92-4.34; P < .001), and living in nonremote areas (eg, remote or very remote vs major cities, OR, 0.23; 95% CI, 0.05-1.04; P = .003).
CONCLUSIONS AND RELEVANCE
In this cohort study, melanomas diagnosed through routine skin checks were associated with significantly lower all-cause mortality, but not melanoma-specific mortality, after adjustment for patient, sociodemographic, and clinicopathologic factors.
Topics: Cohort Studies; Female; Humans; Male; Melanoma; Prospective Studies; Skin; Skin Neoplasms
PubMed: 34730781
DOI: 10.1001/jamadermatol.2021.3884 -
Annals of the Academy of Medicine,... Jun 2021Melanomas in Asians have different clinicopathological characteristics and prognosis from melanomas in Caucasians. This study reviewed the epidemiology and treatment...
INTRODUCTION
Melanomas in Asians have different clinicopathological characteristics and prognosis from melanomas in Caucasians. This study reviewed the epidemiology and treatment outcomes of cutaneous melanoma diagnosed at a tertiary referral dermatology centre in Singapore, which has a multiracial population. The study also determined whether Asians had comparable relapse-free and overall survival periods to Caucasians in Singapore.
METHOD
This is a retrospective review of cutaneous melanoma cases in our centre between 1996 and 2015.
RESULTS
Sixty-two cases of melanoma were diagnosed in 61 patients: 72.6% occurred in Chinese, 19.4% in Caucasians and 3.2% in Indians, with an over-representation of Caucasians. Superficial spreading melanoma, acral lentiginous melanoma and nodular melanoma comprised 37.1%, 35.5% and 22.6% of the cases, respectively. The median time interval to diagnosis was longer in Asians than Caucasians; median Breslow's thickness in Asians were significantly thicker than in Caucasians (2.6mm versus 0.9mm, =0.018) and Asians tend to present at a later stage. The mortality rates for Asians and Caucasians were 52% and 0%, respectively.
CONCLUSION
More physician and patient education on skin cancer awareness is needed in our Asian-predominant population for better outcomes.
Topics: Humans; Melanoma; Prognosis; Retrospective Studies; Singapore; Skin Neoplasms; Treatment Outcome
PubMed: 34195752
DOI: 10.47102/annals-acadmedsg.2020535 -
Dermatology Online Journal Apr 2019Melanoma is an extremely aggressive cancer for which the American Academy of Dermatology currently does not have formal recommendations outlining a timeline from biopsy...
Melanoma is an extremely aggressive cancer for which the American Academy of Dermatology currently does not have formal recommendations outlining a timeline from biopsy to definitive treatment. Our dermatology department investigated our treatment timeline for melanoma. Using the database from our electronic medical record, Epic, we evaluated patients over a one-year period; in total we identified 109 melanomas. We evaluated patient demographics, tumor characteristics, and timelines regarding diagnosis and treatments. There was a statistically significant difference in patient notification of diagnosis and treatment times between stage 1 and stages 2-4 combined (based on the American Joint Committee on Cancer staging system). We found that 84% of melanomas were treated within 4 weeks of diagnosis and 96% within 6 weeks. The lower the stage, the earlier the melanoma was definitively treated; higher stage melanomas had a longer delay to definitive treatment. Herein, we have presented our single institutional experience of the melanoma timeline from diagnosis to definitive treatment and have identified factors that impact timely definitive treatment.
Topics: Aged; Biopsy; Communication; Female; Humans; Male; Melanoma; Middle Aged; Neoplasm Staging; Retrospective Studies; Skin; Skin Neoplasms; Time Factors; Time-to-Treatment
PubMed: 31046916
DOI: No ID Found -
Disease Markers 2022Melanomas are skin malignant tumors that arise from melanocytes which are primarily treated with surgery, chemotherapy, targeted therapy, immunotherapy, radiation...
BACKGROUND
Melanomas are skin malignant tumors that arise from melanocytes which are primarily treated with surgery, chemotherapy, targeted therapy, immunotherapy, radiation therapy, etc. Targeted therapy is a promising approach to treating advanced melanomas, but resistance always occurs. This study is aimed at identifying the potential target genes and candidate drugs for drug-resistant melanoma effectively with computational methods.
METHODS
Identification of genes associated with drug-resistant melanomas was conducted using the text mining tool pubmed2ensembl. Further gene screening was carried out by GO and KEGG pathway enrichment analyses. The PPI network was constructed using STRING database and Cytoscape. GEPIA was used to perform the survival analysis and conduct the Kaplan-Meier curve. Drugs targeted at these genes were selected in Pharmaprojects. The binding affinity scores of drug-target interactions were predicted by DeepPurpose.
RESULTS
A total of 433 genes were found associated with drug-resistant melanomas by text mining. The most statistically differential functional enriched pathways of GO and KEGG analyses contained 348 genes, and 27 hub genes were further screened out by MCODE in Cytoscape. Six genes were identified with statistical differences after survival analysis and literature review. 16 candidate drugs targeted at hub genes were found by Pharmaprojects under our restrictions. Finally, 11 ERBB2-targeted drugs with top affinity scores were predicted by DeepPurpose, including 10 ERBB2 kinase inhibitors and 1 antibody-drug conjugate.
CONCLUSION
Text mining and bioinformatics are valuable methods for gene identification in drug discovery. DeepPurpose is an efficient and operative deep learning tool for predicting the DTI and selecting the candidate drugs.
Topics: Computational Biology; Deep Learning; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Ontology; Humans; Melanoma; Prognosis; Protein Interaction Maps; Technology
PubMed: 35915735
DOI: 10.1155/2022/2461055 -
Pigment Cell & Melanoma Research Jan 2018Melanomas are metabolically heterogeneous, and they are able to adapt in order to utilize a variety of fuels that facilitate tumor progression and metastasis. The... (Review)
Review
Melanomas are metabolically heterogeneous, and they are able to adapt in order to utilize a variety of fuels that facilitate tumor progression and metastasis. The significance of metabolism in melanoma is supported by growing evidence of impact on the efficacy of contemporary therapies for this disease. There are also data to support that the metabolic phenotypes of melanoma cells depend upon contributions from both intrinsic oncogenic pathways and extrinsic factors in the tumor microenvironment. This review summarizes current understanding of the metabolic processes that promote cutaneous melanoma tumorigenesis and progression, the regulation of cancer cell metabolism by the tumor microenvironment, and the impact of metabolic pathways on targeted and immune therapies.
Topics: Animals; Humans; Melanoma; Signal Transduction; Tumor Microenvironment
PubMed: 29049843
DOI: 10.1111/pcmr.12661 -
FEBS Letters Nov 2015Cutaneous melanomas are often difficult to treat when diagnosed in advanced stages. Melanoma cells adapt to survive in extreme environmental conditions and are among the... (Review)
Review
Cutaneous melanomas are often difficult to treat when diagnosed in advanced stages. Melanoma cells adapt to survive in extreme environmental conditions and are among the tumors with larger genomic instability. Here we discuss some intrinsic and extrinsic mechanisms of resistance of melanoma cells to both conventional and target therapies, such as autophagy, adaptation to endoplasmic reticulum stress, metabolic reprogramming, mechanisms of tumor repopulation and the role of extracellular vesicles in this later phenomenon. These biological processes are potentially targetable and thus provide a platform for research and discovery of new drugs for combination therapy to manage melanoma patient treatment.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Cell Proliferation; Drug Resistance, Neoplasm; Humans; Melanoma; Molecular Targeted Therapy
PubMed: 26450371
DOI: 10.1016/j.febslet.2015.09.022 -
International Journal of Molecular... Jan 2024Preferentially Expressed Antigen in Melanoma (PRAME), a member of the cancer/testis antigen family, is central to the field of skin cancer diagnostics and therapeutics.... (Review)
Review
Preferentially Expressed Antigen in Melanoma (PRAME), a member of the cancer/testis antigen family, is central to the field of skin cancer diagnostics and therapeutics. As a nuclear receptor and transcriptional regulator, PRAME plays a critical role in inhibiting retinoic acid signalling, which is essential for cell differentiation and proliferation. Its aberrant overexpression in various malignancies, particularly cutaneous melanoma, is associated with more aggressive tumour phenotypes, positioning PRAME as both a diagnostic and prognostic marker. In melanoma, PRAME is typically highly expressed, in contrast to its weak or absent expression in benign nevi, thereby improving the accuracy of differential diagnoses. The diagnostic value of PRAME extends to various lesions. It is significantly expressed in uveal melanoma, correlating to an increased risk of metastasis. In acral melanomas, especially those with histopathological ambiguity, PRAME helps to improve diagnostic accuracy. However, its expression in spitzoid and ungual melanocytic lesions is inconsistent and requires a comprehensive approach for an accurate assessment. In soft tissue sarcomas, PRAME may be particularly helpful in differentiating melanoma from clear cell sarcoma, an important distinction due to their similar histological appearance but different treatment approaches and prognosis, or in detecting dedifferentiated and undifferentiated melanomas. In non-melanoma skin cancers such as basal cell carcinoma, squamous cell carcinoma, and Merkel cell carcinoma, the variable expression of PRAME can lead to diagnostic complexity. Despite these challenges, the potential of PRAME as a therapeutic target in melanoma is significant. Emerging immunotherapies, including T-cell-based therapies and vaccines targeting PRAME, are being investigated to exploit its cancer-specific expression. Ongoing research into the molecular role and mechanism of action of PRAME in skin cancer continues to open new avenues in both diagnostics and therapeutics, with the potential to transform the management of melanoma and related skin cancers.
Topics: Humans; Male; Antigens, Neoplasm; Biomarkers, Tumor; Diagnosis, Differential; Melanocytes; Melanoma; Prognosis; Skin Neoplasms; Transcription Factors
PubMed: 38338862
DOI: 10.3390/ijms25031582 -
Cancer Control : Journal of the Moffitt... Oct 2013Malignant melanoma is the most fatal type of skin cancer. Traditional melanoma classification has been based on histological subtype or anatomical location. However,... (Review)
Review
BACKGROUND
Malignant melanoma is the most fatal type of skin cancer. Traditional melanoma classification has been based on histological subtype or anatomical location. However, recent evidence suggests that melanoma comprises a group of diseases characterized by distinct molecular mutations. These mutations affect disease behavior but provide unique opportunities for targeted therapy.
METHODS
In this review, several signaling pathways in melanoma are described as well as how mutations of BRAF, NRAS, KIT, GNAQ, and GNA11 genes cause aberrant signaling and malignant transformation.
RESULTS
Multiple genes affecting both the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) pathway are mutated in melanoma. Melanomas harboring the BRAF V600E mutation have demonstrated sensitivity to both RAF and MAPK/extracellular signal regulated kinase (ERK) inhibitors in vitro and in vivo. In addition, KIT-mutant melanomas, often arising from mucosal, acral, and chronically sun-damaged skin surfaces, have shown clinical response to several inhibitors of the type III transmembrane receptor tyrosine kinase KIT. Uveal melanoma, which often harbors GNAQ or GNA11 mutations, may also be sensitive to MAPK/ERK or protein kinase C/PI3K pathway inhibition.
CONCLUSIONS
Emerging knowledge of these molecular alterations has led to clinical advances in patients with melanoma. The study of known mutations and identification of new potential targets must continue in an effort to develop more effective therapies for this disease.
Topics: Animals; Humans; Melanoma; Mutagenesis; Signal Transduction; Skin Neoplasms
PubMed: 24077403
DOI: 10.1177/107327481302000404