Search Results (535)

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

Background: The rising incidence of cutaneous non-melanoma skin cancers underscores the need for individualized reconstruction, particularly for cheek defects that pose distinctive anatomic and functional challenges. This study aimed to analyze reconstructive patterns for cheek skin lesions and to develop a simple, site- and size-based algorithm for small- to medium-sized defects. Methods: We retrospectively reviewed 129 consecutive patients treated between 2022 and 2025 for primary basal cell carcinoma, squamous cell carcinoma, or benign cheek skin tumors. After excision, defects were reconstructed with primary closure, local flaps, or skin grafts. Associations between the largest clinically measured lesion diameter (used as a proxy for the post-excision defect size), anatomical subsite, histopathology, and reconstructive technique were evaluated using ANOVA or Kruskal–Wallis tests, chi-square tests, and Spearman’s correlation. Results: The mean lesion diameter was 19.75 ± 12.93 mm. Reconstruction was performed using local flaps in 62 patients (48.06%), primary closure in 53 (41.09%), and skin grafts in 14 (10.85%). Larger defects were more frequently managed with grafts or flaps (F(2,110) = 4.84, p = 0.010), and lesion size correlated with reconstructive complexity (Spearman’s ρ = 0.229, p = 0.015). Lesion location was also significantly associated with the reconstruction method (χ²(10) = 48.29, p < 0.001; Cramér’s V = 0.44). Margin-negative (R0) excision was achieved in 95.35% of cases, with a low recurrence rate (3.91%) and complication rate (1.56%). Conclusions: Lesion size and anatomical location are key determinants of reconstructive strategy for cheek skin defects. In this cohort, lesions ≤ 20 mm were predominantly managed with primary closure, whereas lesions > 20 mm more frequently required flap reconstruction or skin grafting. This size-based split is cohort-derived and should be interpreted as a pragmatic framework that requires external validation. Full article

Background/Objectives: Non-melanoma skin cancer, which includes cutaneous squamous cell carcinoma (cSCC), ranks as the 5th most common cancer globally with high morbidity and more total deaths than melanoma despite having a lower mortality rate. While most cSCC cases can be treated with surgery, locally advanced, metastatic, and high-risk cSCC tumors are associated with a worse prognosis with higher rates of recurrence and require multimodality therapy. However, there is limited data on animal models of cutaneous squamous cell carcinoma for the use of combinatory immunotherapy and radiation. Methods: In this study, spontaneously generated tumors using DMBA/TPA were treated over three weeks with either IgG control, anti-PD1 antibody monotherapy, 8 Gy of localized radiation, or a combination of anti-PD1 and 8 Gy of radiation followed by anti-PD1 therapy. Results: We found that while anti-PD1 therapy showed a trend toward slowed tumor growth compared to controls, this difference was not statistically significant (p = 0.0775), with most mice showing continued tumor progression. Preliminary histological analysis suggested that anti-PD1 treatment increased CD8+ T cell infiltration, and the addition of radiation further enhanced CD8+ responses but added greater variability. A pathologic review revealed that irradiated tumors were associated with fibroblastic spindle-like cell morphology. Conclusions: This animal model represents a potential preclinical model for studying CSCC with limited responses to immunotherapy to understand potential mechanisms of resistance. Full article

Background: Melanoma and triple-negative breast cancer (TNBC) are the most aggressive skin and breast cancers, often diagnosed at late stages with limited treatment options. The melanoma-associated antigen melanotransferrin (MTf) is overexpressed in these solid tumors, where it drives tumorigenesis, progression, and chemoresistance. Its inhibition correlates with tumor regression, making MTf a promising therapeutic target. This study aimed to develop a novel, selectively targeted antibody–drug conjugate (ADC) against MTf-expressing melanoma and TNBC cancer cells using SNAP-tag fusion protein conjugation technology. Methods: We generated an L49(scFv)-SNAP-tag antibody fusion protein engineered through the genetic fusion of a humanized anti-MTf single-chain variable fragment (scFv) with a SNAP-tag fusion protein capable of site-specific self-labelling with O⁶-benzylguanine (BG) modified substrates in 1:1 stoichiometry. Binding and internalization of the conjugate labeled with BG-Alexa 488 (L49(scFv)-SNAP-Alexa488) were assessed by confocal microscopy and flow cytometry in MTf-overexpressing cell lines. Cytotoxicity was evaluated using the cell viability XTT assay after conjugating the SNAP-fusion protein to the potent monomethyl auristatin-F (BG-AURIF). Results: The L49(scFv)-SNAP-Alexa488 conjugate demonstrated specific binding and internalization into MTf-positive melanoma and TNBC cells. The corresponding ADC, L49(scFv)-SNAP-Linker-AURIF, exerted potent, antigen and dose-dependent cytotoxicity, with IC₅₀ values in the nanomolar range (4.77–34.43 nM). Conclusions: We successfully generated a novel SNAP-tag-based ADC that selectively eliminates MTf-overexpressing tumor cells. This proof-of-concept highlights MTF’s value as a therapeutic target and demonstrates that a smaller-format, non-cleavable linker SNAP-tag-based ADC can achieve potent nanomolar cytotoxicity, supporting further development of MTF-targeted immunotherapies for melanoma and TNBC. Full article

MicroRNAs (miRNAs) have emerged as critical post-transcriptional regulators in melanoma and non-melanoma skin cancers (NMSCs), yet their full biological and clinical significance remains incompletely defined. This review synthesizes current evidence on miRNA dysregulation across basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), Merkel cell carcinoma (MCC), and melanoma, emphasizing their diagnostic, prognostic, and therapeutic relevance. In BCC, distinct miRNA expression signatures differentiate tumor tissue from normal skin and correlate with histopathological subtypes. miR-383-5p, miR-4705, miR-145-5p, and miR-18a show strong diagnostic potential, while downregulation of miR-34a is consistently associated with greater tumor aggressiveness. Subtype-specific profiles further delineate superficial versus infiltrative lesions, highlighting miRNAs as markers of tumor behavior. cSCC similarly demonstrates characteristic miRNA alterations. miR-31 is markedly upregulated during the transition from actinic keratosis to invasive carcinoma, whereas high miR-205 and low miR-203 levels correlate with poor and favorable prognosis, respectively. Regarding MCC, many miRNAs such as miR-375 and miR-182 may present a clinical value for potential biomarkers, as they are upregulated in MCC. Merkel cell carcinoma has also been linked with Merkel cell polyomavirus (MCPyV). Melanoma exhibits a complex miRNA landscape, including oncogenic miR-18a-5p and miR-146a, and tumor-suppressive miR-128-3p. Several miRNAs correlate with metastatic potential, BRAF mutation status, and therapeutic resistance, particularly miR-181a/b, underscoring their potential as predictive biomarkers. Overall, current evidence supports miRNAs as promising diagnostic, prognostic, and predictive biomarkers in cutaneous oncology. Standardized methodologies and large-scale validation remain essential for their integration into routine clinical practice. Full article

Melanoma is among the most lethal forms of skin cancer, where early and accurate diagnosis significantly improves patient survival. Traditional diagnostic pathways, including clinical inspection and dermoscopy, are constrained by interobserver variability and limited access to expertise. Between 2020 and 2025, advances in artificial intelligence (AI) and medical imaging technologies have substantially redefined melanoma diagnostics. This narrative review synthesizes key developments in AI-based approaches, emphasizing the progression from convolutional neural networks to vision transformers and multimodal architectures that incorporate both clinical and imaging data. We examine the integration of AI with non-invasive imaging techniques such as reflectance confocal microscopy, high-frequency ultrasound, optical coherence tomography, and three-dimensional total body photography. The role of AI in teledermatology and mobile applications is also addressed, with a focus on expanding diagnostic accessibility. Persistent challenges include data bias, limited generalizability across diverse skin types, and a lack of prospective clinical validation. Recent regulatory frameworks, including the European Union Artificial Intelligence Act and the United States Food and Drug Administration’s guidance on adaptive systems, are discussed in the context of clinical deployment. The review concludes with perspectives on explainable AI, federated learning, and strategies for equitable implementation in dermatological oncology. Full article

Prostate cancer is the most diagnosed cancer among Canadian men, except non-melanoma skin cancers. Prostate-specific antigen (PSA) screening can enable early detection, but it is not formally recommended in Canada. Nonetheless, opportunistic screening persists, influenced by US practices and some Canadian guidelines that support screening. This study provides a detailed analysis of trends in prostate cancer incidence, mortality, stage distribution, and net survival in the context of evolving PSA screening guidelines. Prostate cancer case (1984–2022) and death (1984–2023) data were primarily from the Canadian Cancer Registry and the Canadian Vital Statistics Death database, respectively. Joinpoint regression identified incidence and mortality trends. Net survival was determined using the Pohar Perme estimator. Following the introduction of PSA screening, the prostate cancer age-standardized incidence rate among men aged 50–74 increased 1.8% annually until 2007 (p = 0.006) before declining at an annualized rate of −5.9% (p = 0.005) until 2014. Among men aged ≥75, incidence declined at −3.2% annually from 1992 to 2015 (p < 0.001). The prostate cancer age-standardized mortality rate (ASMR) among men aged 50–74 fell at an annualized rate of −4.3% between 1994 and 2010 (p = 0.022), but the decline slowed thereafter. The ASMR among men aged ≥75 continuously declined after a peak in 1995, with the greatest change noted before 2012. From 2010 to 2017, stage IV prostate cancer incidence increased across all 10-year age groups, peaking among men aged 60–69 at 4.1% annually (p < 0.001). Among men aged 50–74, the corresponding annualized increase was 3.7% (p = 0.010), while among men aged ≥75, it was 3.1% (p < 0.001). Although stage IV net survival among men aged 50–74 increased from 49.4% in 2010–2011 to 56.6% in 2016–2017, all-stage net survival declined slightly after 2011, concurrent with a shift towards a greater proportion of stage IV cases. Prostate cancer outcomes in Canada reflect US PSA screening recommendations. Organized and thoughtful screening may represent an opportunity to decrease the rising late-stage incidence. Full article

Recent scientific reports have highlighted the physiological role, toxicological effects, and pathophysiological aspects of gasotransmitters, particularly hydrogen sulfide (H₂S), which is recognized as a new member of this family. Endogenous generation of H₂S in the skin occurs through both enzymatic and non-enzymatic pathways. The main enzymes involved in its endogenous production are cystathionine-γ-lyase (CSE), cystathionine-β-synthase (CBS), 3-mercaptopyruvate sulfurtransferase (3-MST) and cysteine aminotransferase. 3-MST and CSE are crucial for maintaining the epidermal barrier. H₂S may play a role in oncogenesis, acting as a gas signaling molecule that disrupts mitochondrial respiration and influences immune modulation, cell proliferation, apoptosis, tumor cell survival, and metastasis. Interestingly, H₂S exhibits dual effects in the biology of skin cancer, promoting tumor growth in some contexts and exerting antitumor activities in others. Data from the European Cancer Information System and Global Cancer Observatory show a significant global increase in skin cancer cases. The most common types of cutaneous malignancies, from both epidemiological and clinical perspectives, are basal cell carcinoma. squamous cell carcinoma, and melanoma. This review aims to evaluate the dysfunctional metabolism of H₂S and the specific profiles of the enzymes that synthesize H₂S in skin cancer. By comparing the roles of H₂S in normal cells with those in cancer cells, we can enhance current understanding of its implications in skin cancer biology. This research paves the way for new clinical strategies, including the development of H₂S-modulatory therapies tailored to the dynamics of tumor progression, which could help overcome therapeutic resistance. Full article

Background/Objectives: Large-scale, country-specific data on skin cancer predictors are scarce in Hungary. The Euromelanoma campaign offers a decade-long opportunity to investigate constitutional, behavioral, and motivational risk factors in a Central European setting through a national cross-sectional analysis. Methods: Between 2009 and 2018, Hungarian participants underwent dermatological screening. Diagnoses of clinically suspicious skin cancers were based on dermoscopic assessment, as histopathological confirmation was not systematically available. Among 18,598 standardized surveys, logistic regression identified independent predictors of clinically suspicious skin cancers overall and separately for melanoma and non-melanoma skin cancers (NMSCs). Results: Clinically suspicious skin cancers were detected in 3.9% of participants (1.7% melanoma, 2.3% NMSC). Strong predictors across all cancer types were atypical nevi (OR 4.75), personal history of NMSC (OR 3.42), and melanoma (OR 1.99). For melanoma, atypical nevi (OR 13.12), prior melanoma (OR 5.95), heavy sunbed use (OR 2.15), and trunk lentigines (OR 1.47) were significant. For NMSC, age (OR 1.08 per year), personal history of NMSC (OR 4.75), family history of melanoma (OR 2.41), and atypical nevi (OR 1.76) were dominant. Screening motivation influenced detection: participants attending for a changing lesion had higher odds of suspicious findings, whereas those attending for routine checks, family/friend history, or “many moles” had lower odds. Conclusions: Over a decade of Euromelanoma screening, atypical nevi, prior skin cancer history, and heavy sunbed use emerged as the strongest predictors of suspicious skin cancers. Participant motivation shaped detection patterns, supporting risk-stratified screening, targeted public education, and stricter regulation of artificial ultraviolet exposure. Full article

Skin cancer is increasing worldwide, with melanoma being its most aggressive and lethal form due to its high metastatic potential. Despite therapeutic advances, drug resistance remains a challenge, highlighting the need to explore new anticancer agents. Leptocarpha rivularis is a native plant of Chile, locally called “Palo negro”, and is traditionally used in medicine by the Mapuche people. L. rivularis produces bioactive germacrene sesquiterpenoids with cytotoxic, antioxidant, anti-inflammatory and anti-angiogenic properties. This study reports for the first time the isolation of ovatifolin from aerial parts of L. rivularis and its identification by NMR and X-ray diffraction, together with its antiproliferative activity against two melanoma cell lines. The results show that ovatifolin has cytotoxic activity against the cell lines A2058 and A375, with an IC₅₀ of 27.6 (90.2 µM) and 18.4 µg/mL (60.1 µM), respectively, evaluated by live-cell IncuCyte^® analysis. Moreover, ovatifolin arrests colony formation in a clonogenic assay, with an IC₅₀ of 3.26 (10.6 μM) and 3.65 µg/mL (11.9 μM) in these same cell lines. Therefore, ovatifolin increased intracellular ROS and decreased the mitochondrial membrane potential (ΔΨ m). Cell death studies using Annexin V showed that its cytotoxic activity is partially caused by non-specific apoptosis, which was corroborated by the caspase inhibitor Z-VAD with an incomplete recovery of the cell death process. Full article

Background: Non-melanoma skin cancer (NMSC) is the most frequent cancer in fair-skinned populations and represents a growing public health concern due to its impact in terms of morbidity and treatment costs. While some meta-analyses have investigated cigarette smoking as a risk factor for NMSC, less is known about its prognostic implications in patients with NMSC. This systematic review and meta-analysis aims to fill this gap by assessing the association between smoking habits and survival in patients with NMSC. Methods: A systematic search was conducted in PubMed and EMBASE up to 25 February 2025, to identify prospective studies of patients with histologically confirmed NMSC that evaluated the association between smoking habits and survival. Study-specific hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were pooled using random effects meta-analysis models. Results: A total of five studies published between 2015 and 2022 were included. The meta-analysis revealed that being a current or ever smoker at diagnosis was associated with a worse overall survival (summary HR 2.42, 95% CI 1.91–3.06). A similar result was observed when smoking exposure was assessed in terms of pack-years or number of cigarettes per day (summary HR 2.44, 95% CI 2.02–2.93). Conclusions: Our findings indicate that cigarette smoking is a negative prognostic factor in these patients, despite the generally excellent prognosis of NMSC. It is reasonable to assume that this unfavourable effect is largely due to the increased risk of developing other life-threatening conditions, in which smoking plays a causal role. These results underscore the clinical relevance of systematically integrating smoking cessation counselling into the routine management of patients with NMSC. Full article

Melanoma, in advanced stages, is the most invasive type of skin cancer, with currently available treatments showing limited efficiency. The number of melanoma cancer cases is expected to increase in the coming years, emphasizing the need for more efficient therapeutic strategies. The present study aimed to evaluate the potential of β-blockers, commonly used to treat cardiac conditions, to be repurposed for the treatment of melanoma. The effects of non-selective β-blockers (carvedilol and propranolol), β1 selective blockers (atenolol and metoprolol) and antineoplastics drugs (cisplatin and 5-fluorouracil) on the A375 melanoma cell line were studied, individually and in combined exposures, by assessing cell viability over a 72 h period. The 72 h half-maximal inhibitory concentrations (IC₅₀s) determined for A375 cells allow the ranking of toxicity as: cisplatin (2.46 (1.87–3.38) μM) > 5-fluorouracil (4.77 (4.48–5.07) μM) > carvedilol (16.91 (15.47–18.99) μM) > propranolol (58.03 (57.08–59.11) μM) > atenolol and metoprolol (β1 selective blockers that exhibited no significant effect on the cell’s viability). The effects of combined exposures were also studied. Metoprolol and carvedilol exhibited synergistic interactions with cisplatin at specific concentrations. Overall, the data highlight the concentration-dependent nature of mixture effects and support the potential application of β-blockers melanoma treatment. Full article

Background/Objectives: The anatomical complexity of the auricular region poses a unique challenge for contact interventional radiotherapy (IRT, modern brachytherapy), especially in maintaining close conformity between the applicator and skin surface. Air gaps can arise due to the irregular shape of the ear, potentially compromising dose coverage. This study evaluates the dosimetric impact of air gaps in HDR IRT for non-melanoma skin cancer (NMSC) of the ear. Methods: Ten patients treated with contact IRT using alginate as supporting material were retrospectively analyzed. Treatment plans were recalculated using both the TG-43 and the TG-186 formalism. CTV coverage and organ-at-risk dose parameters were evaluated within the two formalisms. Results: CTV coverage was comparable between algorithms (mean V95% 96.2% vs. 94.4%, V100% 89.6% vs. 86.7%, and V150% 2.6% vs. 2.5% for TG-43 vs. TG-186; p > 0.05), while the ipsilateral eye D2cc decreased from 4.0% (TG-43) to 3.2% (TG-186). In silico simulations showed that increasing air gaps reduced skin dose progressively (up to ~15% at 5 mm), whereas alginate thickness produced only a mild dose increase (<5%) across the tested range. Overall, small air pockets (<1 mm) did not substantially alter global dosimetric metrics, although local underdosage may occur at gap locations. Conclusions: This study underscores the importance of accounting for material heterogeneities and geometric uncertainties in anatomically complex regions through advanced dose calculation algorithms. Full article

Background/Objectives: Prior studies have reported a complex interplay between Parkinson’s disease (PD) and malignancy. Although patients with PD often present a lower general risk for several types of cancer, some forms—including melanoma—show elevated frequency. The present work aimed to evaluate the occurrence of cancers other than melanoma among individuals with sporadic and genetic PD. Methods: We examined medical histories from 1888 participants with PD and 438 healthy controls (HCs) using the Parkinson’s Progression Markers Initiative (PPMI) dataset, with a focus on neoplastic disease. In cases with positive cancer history, genetic information was additionally assessed [carriers of mutations in the most prevalent PD-related genes were evaluated]. Results: Our results demonstrate that cancer incidence was antecedent to PD diagnosis for the majority of PD patients, while the most common cancer types apart from malignant melanoma were non-melanoma skin cancer and prostate cancer. Conclusions: Regarding genetic PD patients, the most common cancer types in the LRRK2 and GBA1 groups were skin cancer and lymphoma, while PRKN/PARK2 carriers appeared with an overall increased incidence of cancer. No statistically significant results were observed comparing cancer incidence in PD patients to that in healthy control individuals. Interesting results were obtained by dividing the patients by gender, showing increased cancer risk in female PD patients and female LRRK2 carriers, along with increased breast cancer risk in female PD patients compared to healthy controls. Full article

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin malignancy in the world, representing approximately 20% of all skin cancers. Immunosuppression is a well-established risk factor, contributing not only to the development of new cSCC lesions but also to more aggressive disease and increased mortality. Despite the National Comprehensive Cancer Network (NCCN) and the American Joint Committee on Cancer (AJCC) 8th edition updates recognizing immunosuppression as a risk factor for cSCC, standardized management protocols for these high-risk patients remain limited. As a result, treatment of this already high-risk group remains a significant challenge and highlights the need for dedicated research and attention to improve outcomes in this patient population. This review explores the current knowledge regarding cSCC in IS patients, outlines key gaps in the knowledge, and highlights recent clinical trials to further guide the evaluation and management of these patients. Full article