Search Results (1,492)

Background/Objectives: Melanoma remains one of the most malignant types of skin cancer with rising incidence numbers, despite the progress made in the prevention and management of the disease. Recent technological advancements, such as developments in the field of molecular biology, imaging, and artificial intelligence (AI), have led to a paradigm shift in the diagnosis, assessment, and management of melanoma. The current review aims to integrate current research on melanoma, moving beyond the boundaries of conventional histological analysis. Methods: This is a critical appraisal narrative review that focuses on recent studies in the areas of translation research and digital health with regard to melanoma. This research particularly targeted recent studies within the last five years, with landmark studies implicated when appropriate. Evidence was synthesized within the major categories that include epidemiology, early diagnosis, histopathology, predictive biomarkers, genetic/epigenetic changes, AI-assisted diagnostic platforms, and novel therapeutic platforms & targets. Results: Early detection techniques, innovative imaging, and biomarker-guided risk adjustment can improve diagnostic accuracy and prognostic stratification. The potential of AI in dermoscopy, digital pathology, and decision analytical systems is evident, although validation, bias, and integration issues need to be addressed. Advances in immunotherapy, targeted therapies, and novel molecular/immunological targets are expanding and facilitating integrated and personalized management. Conclusions: There is a trend in melanoma research to shift towards an integrated diagnostic platform that involves the use of AI, molecular characterization, and clinical inputs to enable more accurate and personalized diagnoses. To realize this potential, there is a need to validate, collaborate, and address ethics and implementation. Full article

Background: The precise segmentation and classification of dermoscopic images remain prominent obstacles in automated skin cancer evaluation due, in part, to variability in lesions, low-contrast borders, and additional artifacts in the background. There have been recent developments in foundation models, with a particular emphasis on the Segment Anything Model (SAM)—these models exhibit strong generalization potential but require domain-specific adaptation to function effectively in medical imaging. The advent of new architectures, particularly Vision Transformers (ViTs), expands the means of implementing robust lesion identification; however, their strengths are limited without spatial priors. Methods: The proposed study lays out an integrated foundation-model-based framework that utilizes SAM-Adapter-fine-tuning for lesion segmentation and a ViT-based classifier that incorporates lesion-specific cropping derived from segmentation and cross-attention fusion. The SAM encoder is kept frozen while lightweight adapters are fine-tuned only, to introduce skin surface-specific capacity. Segmentation priors are incorporated during the classification stage through fusion with patch-embeddings from the images, creating lesion-centric reasoning. The entire pipeline is trained using a joint multi-task approach using data from the ISIC 2018, HAM10000, and PH2 datasets. Results: From extensive experimentation, the proposed method outperforms the state-of-the-art segmentation and classification across the dataset. On the ISIC 2018 dataset, it achieves a Dice score of 94.27% for segmentation and an accuracy of 95.88% for classification performance. On PH2, a Dice score of 95.62% is achieved, and for HAM10000, an accuracy of 96.37% is achieved. Several ablation analyses confirm that both the SAM-Adapters and lesion-specific cropping and cross-attention fusion contribute substantially to performance. Paired t-tests are used to confirm statistical significance for all the previously stated measures where improvements over strong baselines indicate a $p<0.01$ for most comparisons and with large effect sizes. Conclusions: The results indicate that the combination of prior segmentation from foundation models, plus transformer-based classification, consistently and reliably improves the quality of lesion boundaries and diagnosis accuracy. Thus, the proposed SAM-ViT framework demonstrates a robust, generalizable, and lesion-centric automated dermoscopic analysis, and represents a promising initial step towards clinically deployable skin cancer decision-support system. Next steps will include model compression, improved pseudo-mask refinement and evaluation on real-world multi-center clinical cohorts. Full article

Melanoma is a type of skin cancer with an increasing incidence rate worldwide and a high mortality rate. In addition to known risk factors, such as UV exposure and genetic predisposition, researchers are paying more attention to the role of diet, micronutrients, and vitamins in preventing melanoma. This review discusses the effects of selected vitamins (D, A, C, and E), trace elements, and bioactive compounds (polyphenols and omega-3 fatty acids) on biological processes related to melanoma development. The review considered both antioxidant and immunomodulatory effects, as well as effects on DNA repair and photoprotection. The significance of polymorphisms of genes encoding receptors and enzymes that metabolize the compounds studied was also analyzed. The results suggest that maintaining adequate levels of these substances may promote melanoma prevention, particularly among individuals at risk. However, caution in the use of supplementation is necessary due to the possible biphasic effects of some micronutrients. Further clinical trials are needed to develop effective, safe prevention strategies based on micronutrients and vitamins. Full article

Background/Objectives: Melanoma is the most lethal cutaneous neoplasm, with Breslow thickness being a key prognostic factor. This retrospective cohort study aimed to assess the impact of screening frequency and diagnostic methods on tumour stage at diagnosis and to explore implications for risk-adapted strategies. Methods: Between 2017 and 2024, 475 cases of melanoma were diagnosed in 397 patients. Screening frequency, diagnostic method, and patient risk were analyzed in relation to tumour stage. Results: Compared with first-visit cases, patients who underwent screening within two years prior to diagnosis were more often diagnosed with melanoma in situ (32.6% vs. 44–51%; p < 0.05) and had thinner invasive tumours (0.68–0.73 mm vs. 1.8 mm; p ≤ 0.001), though no differences were seen between screening frequencies. Full-body examination was associated with more in situ melanomas (46% vs. 34%; p = 0.016) and thinner invasive tumours (0.92 vs. 2.05 mm; p = 0.2) compared with lesion-directed screening, but this effect disappeared after excluding first-visit cases. Invasive melanomas diagnosed by mole mapping were significantly thinner than by dermoscopy (0.55 vs. 1.07; p = 0.035). In high-risk patients, tumour thickness decreased with more frequent visits (0.905 mm without screening vs. 0.40–0.55 mm with ≥1 visit; p = 0.001). Moreover, mole mapping identified thinner melanomas in the high-risk group compared with dermoscopy (0.47 vs. 0.60 mm; p = 0.02). Conclusions: Screening is associated with thinner melanomas and more in situ diagnoses. Digital mole mapping offers additional benefits, with high-risk patients profiting most, while low-risk individuals could be managed with less resource-intensive approaches. These findings support risk-adapted screening strategies focusing on intensive, digitally supported modalities for high-risk groups. Full article

The incidence of melanoma and non-melanoma skin cancers (NMSCs) is increasing worldwide. While NMSCs are more common, melanoma remains the most challenging because of its higher aggressiveness. Although the use of sunscreens is key in high-risk populations, it provides limited protection, which highlights the need for alternative solutions. In this review, we discuss current evidence on chemopreventive therapies, as well as their efficacy and adverse events, including immunocompetent and immunosuppressed patients. Acitretin, nicotinamide, 5-fluorouracil, and photodynamic therapy have shown overall promising results in actinic keratosis and squamous cell carcinoma. Nevertheless, more research is needed to establish their efficacy, particularly in melanoma, Merkel cell carcinoma, and cutaneous lymphoma, due to their higher mortality rates. Full article

Cutaneous melanoma is one of the most aggressive skin cancers. Over the years, multiple studies have focused on identifying novel treatment strategies, with increasing attention directed toward immune-modulating mechanisms within the tumor microenvironment. Among these, ATP-binding cassette transporters and stem-associated pathways have been shown to influence drug response and immune escape. ABCB5 is a gene with multiple isoforms that significantly influences the immune response. In melanoma, the ABCB5α isoform is predominantly expressed, particularly in tumor stem-like cells where it promotes chemoresistance through active drug efflux. ABCB5 has also been linked to the regulation of PI3K/Akt, BCL-2, and miR-145-associated pathways. Moreover, ABCB5-positive cells contribute to the formation of an immunosuppressive microenvironment by secreting cytokines (IL-6, IL-8, TGF-β) and expressing immune checkpoint ligands, such as PD-L1, thereby favoring tumor progression and a poor prognosis. This review integrates current data on the molecular and microenvironmental mechanisms underlying melanoma progression and therapy resistance, and positions ABCB5 within the broader landscape of melanoma resistance mechanisms, emphasizing both its potential and its current limitations as a biomarker and therapeutic target. Full article

Geodiamolides are depsipeptides previously isolated from marine sponges that are able to disrupt cytoskeleton microfilaments, inhibit cell migration and invasion, and reverse the malignant phenotype of human breast cancer cell lines to polarized spheroid-like structures. Such cytotoxicity to different cellular targets in breast cancer cells suggests that these molecules might also act in other cancer types such as non-melanoma skin cancer (NMSC), one of the cancer types with high incidence worldwide. Thus, the goal of this work was to study the effects of the marine sponge depsipeptides Geodiamolide A and H (Geo A and Geo H) in human squamous cell carcinoma (A431, NMSC) in order to investigate their effects on cell proliferation and cell death. While no significant statistical difference was observed after Geo H treatment, an expressive dose-dependent reduction in A431 cell viability (IC₅₀ of 368 nM, MTT assay; p < 0.05) and proliferation pattern (real-time cell analysis assay) was shown after 48 h exposure with Geo A. The cell proliferation blockade was confirmed after 24 h of Geo A treatment at 500 nM, with a 46% (p < 0.0001) reduction in the total number of cells (cell counting) and G2/M phase cell cycle arrest. Other cytotoxic evidence such as DNA fragmentation, phosphatidylserine exposure (flow cytometry), and time-dependent plasma membrane damage (Trypan Blue) suggested cell death by apoptosis. Therefore, Geo A showed both cytostatic and cytotoxic effects on A431 cells. Taken together, these data point out Geo A as a promising therapeutic molecule for NMSC treatment and is the first depsipeptide (marine or terrestrial), to our knowledge, to target this type of cancer cell. Full article

Background/Objectives: Colorectal cancer (CRC) is a major public health challenge in Brazil, characterized by marked regional disparities. Although national legislation mandates that treatment begin within 60 days after diagnosis, compliance remains inconsistent, particularly within the Unified Health System (SUS). This study aimed to analyze the time to treatment initiation for colon (C18) and rectal (C20) cancer in Brazil from 2013 to 2024, assessing regional inequalities, temporal trends, and factors associated with treatment delays. Methods: We conducted an ecological study using secondary data from the Ministry of Health’s PAINEL-Oncologia platform, which integrates information from SIA/SUS, SIH/SUS, and SISCAN. Records of patients diagnosed with colon and rectal cancer (ICD-10 C18–C20) were evaluated. Temporal trends were analyzed using Joinpoint regression, and factors associated with delayed treatment initiation (>60 days) were identified through multiple logistic regression models. Results: Persistent discrepancies were observed between diagnostic and treatment trends from 2013 to 2024, with the Annual Percent Change (APC) for diagnosis exceeding that for treatment, particularly among adults aged 55–69 years. The Southeast and South regions accounted for over 70% of all diagnosed cases, starkly contrasting with the less than 25% in the North and Northeast. More than 50% of patients across all clinical stages initiated treatment after the legally mandated 60-day period. Women with rectal cancer had a 28% higher risk (RR = 1.28) of being diagnosed at stage IV. Chemotherapy was the predominant initial therapeutic modality, while the need for combined chemo-radiotherapy was associated with markedly elevated risk ratios for delay (e.g., RR = 26.53 for stage IV rectal cancer). Treatment initiation delays (>60 days) were significantly associated with residence in the North/Northeast regions, female sex (for rectal cancer), advanced-stage disease, and complex therapeutic regimens. Conclusions: The study demonstrates persistent regional inequalities and highlights a substantial mismatch between diagnostic capacity and therapeutic availability in Brazil. These gaps contribute to treatment delays and reinforce the need to strengthen and expand oncological care networks to ensure equitable access and improve outcomes, particularly in underserved regions. Full article

Skin cancer (SC) is the most prevalent malignancy worldwide, with subtypes varying in aggressiveness: basal cell carcinoma tends to be locally invasive, squamous cell carcinoma has a higher metastatic risk, and melanoma remains the deadliest form. Current treatments such as surgery, radiotherapy, and systemic chemotherapy are associated with aesthetic and functional morbidity, recurrence, and/or systemic toxicity. Although targeted therapies and immunotherapies offer clinical benefits, their high cost and limited accessibility underscore the need for innovative, affordable alternatives. Metal-based compounds (metallopharmaceuticals) are promising anticancer agents due to their ability to induce oxidative stress, modulate redox pathways, and interact with DNA. However, clinical translation has been limited by poor aqueous solubility, rapid degradation, and low skin permeability. This review discusses the most recent preclinical findings on gold, silver, platinum, palladium, ruthenium, vanadium, and copper complexes, mainly in topical and systemic treatments of SC. Advances in chemical and physical enhancers, such as hydrogels and microneedles, and in drug delivery systems, including bacterial nanocellulose membranes and nanoparticles, as well as liposomes and micelles, for enhancing skin permeation and protecting the integrity of metal complexes are also discussed. Additionally, we examine the contribution of photodynamic therapy to SC treatment and the use of mathematical and computational modeling to simulate skin drug transport, predict biodistribution, and support rational nanocarrier design. Altogether, these strategies aim to bridge the gap between physicochemical innovation and clinical applicability, paving the way for more selective, stable, and cost-effective SC treatments. Full article

Melanoma is the deadliest form of skin cancer, characterized by high metastatic potential and intrinsic heterogeneity. In addition to genetic mutations such as BRAF^V600E^ and NRAS, lipid metabolic reprogramming has emerged as a critical factor in tumor progression and therapy resistance. Lipid metabolism supports melanoma cell survival, phenotypic switching, immune evasion, and resistance to targeted therapies and immunotherapy, while also modulating susceptibility to ferroptosis. This review summarizes current knowledge on lipid dysregulation in melanoma, highlighting alterations in fatty acid synthesis, desaturation, uptake, storage, and oxidation, as well as changes in phospholipids, sphingolipids, cholesterol, and bioactive lipid mediators. These lipid pathways are tightly regulated by oncogenic signaling networks, including MAPK and PI3K–AKT–mTOR pathways, and are influenced by tumor microenvironmental stressors such as hypoxia and nutrient limitation. Advances in lipidomics technologies, particularly mass spectrometry-based approaches, have enabled comprehensive profiling of lipid alterations at bulk, spatial, and single-cell levels, offering new opportunities for biomarker discovery and therapeutic stratification. Targeting lipid metabolic vulnerabilities represents a promising strategy to improve melanoma diagnosis, prognosis, and treatment efficacy. Full article

Melanoma is an aggressive skin cancer that continues to present major therapeutic difficulties. Although targeted drugs and immune checkpoint inhibitors have improved outcomes, resistance and treatment-related toxicity limit long-term benefit. In recent years, nanotechnology has been explored as a way to improve how drugs are delivered and to achieve greater tumor selectivity. Among available nanocarriers, liposomes have attracted particular interest. Built from lipid bilayers, they can carry both hydrophilic and hydrophobic molecules, and they are generally well tolerated. Importantly, their surface can be modified with polymers or targeting ligands to direct the carrier more selectively to melanoma cells. Experimental models show that liposomal drug formulations can increase concentrations in tumor tissue while limiting distribution to healthy organs. They have also been used successfully to combine different types of agents, chemotherapies, immunomodulators, and nucleic acids, within a single delivery system. These findings suggest genuine potential to address several of the shortcomings of conventional treatments. Although translation to the clinic is slowed by challenges such as formulation stability and large-scale production, liposomes represent an important step toward safer and more effective melanoma therapy within the broader field of oncologic nanotechnology. Full article

Melanoma is highly dangerous and can spread rapidly to other parts of the body. It has an increasing fatality rate among different types of cancer. Timely detection of skin malignancies can reduce overall mortality. Therefore, clinical screening methods require more time and accuracy for diagnosis. An automated, computer-aided system would facilitate earlier melanoma detection, thereby increasing patient survival rates. This paper identifies melanoma images using a Convolutional Neural Network. Skin images are preprocessed using Histogram Equalization and Gabor transforms. A Gabor filter-based Convolutional Neural Network (CNN) classifier trains and classifies the extracted features. We adopt Gabor filters because they are bandpass filters that transform a pixel into a multi-resolution kernel matrix, providing detailed information about the image. This study suggests a method with accuracy, sensitivity, and specificity of 98.58%, 98.66%, and 98.75%, respectively. This research supports SDGs 3 and 4 by facilitating early melanoma detection and enhancing AI-driven medical education. Full article

Cutaneous melanoma is a highly aggressive skin cancer prone to relapse and metastasis. Surgery is often curative when combined with early screening and prevention. However, in recurrent or advanced disease, the development of new targeted and immune therapies has demonstrated promising clinical outcomes, although the acquisition of resistance limits their effectiveness. Thus, new therapeutic approaches are needed. Emerging data indicate that the Hedgehog (Hh) pathway, which is essential for embryonic development, is aberrantly reactivated in melanoma and may represent a promising therapeutic target. Here, we demonstrate its chronic up-modulation in a panel of patient-derived cell lines and, by investigating the underlying molecular mechanisms, we excluded mutations in the principal components of the pathway. We observed reduced PTCH1 and SUFU repressors expression and GLI2 upregulation as common melanoma features. At the same time, copious SHH release, the principal PTCH1 ligand, evidenced autocrine Hh signaling activation. Consistently, a tendency of greater level of this factor resulted higher in the blood of patients compared to controls, confirming the relevance of ligand-dependent trigger in melanoma. The therapeutic potential of inhibiting the Hh pathway is highlighted by the reduced proliferation and migration observed in the presence of clinically approved pharmacological Hh antagonists. Profiling inflammatory mediators revealed significant modulation upon treatment with SMO inhibitors, possibly affecting chemotactic and immune functions. Collectively, these findings provide deeper insight into the role of the Hh pathway in melanoma and support the potential repurposing of Hh inhibitors as therapeutic agents for melanoma. Full article

Background/Objectives: Actinic keratoses (AKs), also known as solar keratoses, are considered premalignant skin lesions that can evolve into squamous cell carcinoma (SCC). Among the available options, 5-fluorouracil (5-FU) remains a cornerstone. Methods: This study is a retrospective analysis of our database of the non-melanoma skin cancer outpatient clinic. The main objective was to evaluate patients treated with 4% 5-FU cream for AK lesions. The efficacy of 4% 5-FU was evaluated retrospectively by measuring the percentage of patients who achieved complete clearance. A secondary efficacy measure was the percentage of partial clearance, defined as at least a 75% reduction in lesion count. Additionally, the study aimed to assess the safety of 4% 5-FU cream. Results: We included 150 patients clinically diagnosed with AK, treated with 4% 5-FU cream and evaluated 432 lesions. Complete clearance of lesions was observed in 138 patients (92%) with partial clearance in 12 patients (8%). At 12 months, the recurrence rate was 11%. Conclusions: Based on our analysis, 4% 5-FU cream is an effective and well-tolerated treatment for AKs, particularly in patients with extensive field cancerization. While local skin reactions are a natural part of its mechanism, they are manageable and do not outweigh clinical benefits. Full article

Alpha-1 antitrypsin (AAT) is a serine protease inhibitor with potent anti-inflammatory and immunomodulatory properties, but its role in cancer is context-dependent across tumor types. We integrated transcriptomic analyses of human melanoma cohorts, in vivo studies using AAT-transgenic (hAAT-TG) mice, and in vitro assays in murine and human melanoma cells to define the biological functions of AAT in melanoma. SERPINA1 expression increased progressively from normal skin to nevi and metastatic melanoma, yet higher intratumoral levels correlated with improved overall survival in metastatic disease. In hAAT-TG mice, melanoma growth was markedly inhibited compared with wild-type controls, and the inhibitory effect required CD8⁺ T cells and was enhanced by CD4⁺ T-cell depletion, demonstrating that AAT promotes cytotoxic T-cell activity while attenuating regulatory T-cell suppression. Histologic analysis showed heavily pigmented tumors in hAAT-TG mice. In vitro, hAAT upregulated melanocytic differentiation markers (MITF, TYR, PMEL, MART-1) and increased melanin production in murine and human melanoma lines, suggesting enhanced tumor immunogenicity. In conclusion, hAAT exerts antitumor effects in melanoma indirectly by reprogramming the tumor microenvironment toward differentiation and immune activation. These findings highlight a previously unrecognized role for AAT as a dual immunoregulatory and differentiation-promoting factor and support AAT as a potential immunoregulatory adjuvant in melanoma. Full article