Search Results (230)

Non-melanoma skin cancer (NMSC), comprising basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), represents the most common type of cancer worldwide, particularly among Caucasians. While BCC is locally invasive with minimal metastatic potential, cSCC is a highly aggressive tumor with a significant potential for metastasis, particularly in elderly populations. Tumor development and progression and the metastasis of cSCC are influenced by a complex interplay between tumor cells and the tumor microenvironment. Recent research highlights the importance of various immune cell subsets, including T cells, tumor-associated macrophages (TAMs), and dendritic cells, in influencing tumor progression, immune evasion, and treatment resistance. This review outlines key regulatory mechanisms in the immune tumor microenvironment (TME) of cSCC and explores the role of cytokines, immune checkpoints, and stromal interactions. We further discuss the relevance of three-dimensional (3D) in vitro models such as spheroids, organoids, and tumor-on-chip systems as tools to mimic immune–tumor interactions with higher physiological relevance, such as macrophage activation and polarization against cSCC cells. Globally, 3D models offer new opportunities for immunotherapy screening and mechanistic studies. Understanding the immune landscape in cSCC through advanced modeling techniques holds strong clinical potential for improving diagnostic and therapeutic strategies. Full article

Malignant cutaneous melanoma is among the most aggressive forms of skin cancer, characterized by high metastatic potential and frequent resistance to standard therapies. Hydroxytyrosol, a phenolic compound derived from extra virgin olive oil, has shown promising anticancer properties in various models, yet its effects in 3D melanoma systems remain poorly understood. In this study, we used paired 3D spheroid models of non-tumorigenic (HEMa) and melanoma (C32) to assess the therapeutic potential of hydroxytyrosol. To evaluate the anti-tumoral effect of hydroxytyrosol, we performed cytotoxicity, metastasis, invasiveness, cell cycle arrest, apoptotic, and proteomic assays. Hydroxytyrosol treatment significantly impaired spheroid growth, reduced cell viability, and induced cell cycle arrest and apoptosis in C32 spheroids, with minimal cytotoxicity observed in HEMa models. Proteomic profiling further demonstrated that hydroxytyrosol selectively downregulated a network of oncogenic proteins, including ERBB2, ERBB3, ERBB4, VEGFR-2, and WIF-1, along with suppression of downstream PI3K-Akt and MAPK/ERK signaling pathways. In conclusion, compared to dabrafenib, hydroxytyrosol exerted a broader range of molecular effects and was more selective toward tumor cells. These findings support the use of hydroxytyrosol as a multi-targeted agent capable of attenuating melanoma progression through suppression of kinase signaling and tumor-stromal interactions. Full article

Background/Objectives: The gold standard of treatment for both melanoma and non-melanoma skin cancers is wide surgical resection to obtain oncological radicality, which occasionally results in functional or aesthetic impairment, potentially affecting quality of life. Despite the increased complexity of the technique, extended duration of hospitalization, and prolonged surgical operative times, microsurgery can facilitate the reconstruction of locally invasive skin cancers following ablative surgery and may yield superior functional and aesthetic outcomes. Consequently, microsurgical reconstruction is more likely to be necessary if a large skin tumor requires excision. However, the impact of this extensive and complex procedure on patients with skin cancer has not yet been fully elucidated. The objective of this research was to critically analyze the utilization of free flap reconstruction subsequent to skin cancer therapy. Through a comprehensive examination of published data, this study aimed to assess the potential benefits and drawbacks associated with this reconstructive approach. Methods: A systematic review of studies that were published from January 2004 to May 2024 was conducted using the MEDLINE online database search. To present an evidence summary and provide a systematic approach and quality assessment, the GRADE^® rating was applied to the results. Results: This review summarizes the oncological and clinical data, including previous interventions, adjuvant and neoadjuvant therapies, nodal status, distant metastasis, and follow-up time. Surgical outcome parameters such as healing time, flap survival, revision rate success, and minor and major complications were documented. Along with the findings, a quality assessment of the studies was also provided. Conclusions: This systematic review underscores the extensive use and efficacy of microsurgery for reconstruction after skin cancer excision; however, the literature remains limited by inconsistent reporting of oncological outcomes and the lack of a standardized approach to evaluate the impact of free flap reconstruction on both immediate and long-term cancer-specific results. Full article

This narrative review examines the efficacy, cost-effectiveness, and aesthetic outcomes of Mohs micrographic surgery (MMS) compared to standard excision for treating non-melanoma skin cancers (NMSCs). A comprehensive literature search was conducted across multiple databases, including PubMed, Scopus, and Cochrane Library, covering studies published from 2000 to 2024. Key terms such as “Mohs Micrographic Surgery,” “non-melanoma skin cancer,” “recurrence rates,” “cost-effectiveness,” and “aesthetic outcomes” were utilized. Inclusion criteria encompassed peer-reviewed articles, clinical trials, and observational studies focusing on MMS and standard excision outcomes. Exclusion criteria included studies with inadequate data or those not published in English. The review highlights the superior oncologic outcomes of MMS, its cost-effectiveness over the long term, and comparable aesthetic results to standard excision principally. Methods: This narrative review was conducted following established guidelines for reporting narrative reviews. A systematic search strategy was employed across selected databases, with the last search conducted in May 2025. The search terms used were “Mohs Micrographic Surgery,” “non-melanoma skin cancer,” “recurrence rates,” “cost-effectiveness,” and “aesthetic outcomes.” Studies included were published between 2000 and 2024, in English, and provided data on the specified outcomes. Results: The majority of studies indicated that MMS offers superior recurrence-free survival rates compared to standard excision. Regarding cost-effectiveness, MMS was found to be more economical over the long term due to reduced recurrence rates and the need for fewer re-excisions. Aesthetic outcomes were comparable between MMS and standard excision, with both methods yielding satisfactory results. Discussion: The findings of this review support the use of MMS as a preferred treatment for high-risk NMSCs, particularly in cosmetically sensitive areas. While MMS may involve higher initial costs, its long-term cost-effectiveness and superior oncologic outcomes justify its use. The aesthetic outcomes associated with MMS are comparable to those of standard excision, making it a viable option for patients concerned with cosmetic results. Limitations: This review acknowledges several limitations, including the heterogeneity of study designs and potential selection biases inherent in the included studies. Additionally, the absence of randomized controlled trials comparing MMS and standard excision directly limits the strength of the conclusions drawn. Conclusions: This narrative review underscores the advantages of MMS in treating high-risk NMSCs, particularly in terms of recurrence rates and long-term cost-effectiveness. While both MMS and standard excision offer comparable aesthetic outcomes, the superior oncologic results of MMS make it a preferable option in certain clinical scenarios. Full article

Skin cancer, including melanoma and non-melanoma cancers (basal and squamous cell carcinomas), is the most common type of cancer. UV radiation, family history, and genetic predisposition are the main risk factors. Although surgical excision is the standard treatment, essential oils are attracting growing interest for their anti-cancer effects. This study tested the effects of Juniperus excelsa M. Bieb. (Cupressaceae), Lavandula vera DC. (Lamiaceae), and Salvia fruticosa (Mill). (Lamiaceae) essential oils extracted from Middle Eastern medicinal plants on HaCaT (normal), A5 (benign), and II4 (low-grade malignant) keratinocytes. Essential oils were extracted from Juniperus excelsa, Lavandula vera, and Salvia libanotica using steam distillation and then were chemically analyzed. The oils were sterilized, dissolved in DMSO, and prepared at concentrations of 0.75, 0.5, and 0.25 mg/mL. Human keratinocyte (HaCaT), benign (A5), and malignant (II4) cell lines were cultured in DMEM and treated with the essential oils for 24 or 48 h. Cell viability was assessed using the Trypan Blue Exclusion Test, while cell proliferation was evaluated using the MTT assay. Statistical analysis was performed using ANOVA with appropriate post hoc tests, considering p < 0.05 as significant. The results show that J. excelsa is cytotoxic but lacks selectivity, limiting its efficacy. In contrast, L. vera and S. fruticosa preferentially target malignant cells, particularly at low concentrations, while sparing normal cells. These oils have dose-dependent anticancer effects, with L. vera efficacy increasing as the concentration increases. In conclusion, L. vera and S. fruticosa are promising candidates for the treatment of skin cancer, although further in vivo studies are required. Full article

Background/Objectives: Non-melanoma skin cancer (NMSC) is among the most common cancers in the United States, with solar ultraviolet (UV) radiation being a primary etiological factor. T-LAK cell-originated protein kinase (TOPK), a serine/threonine kinase activated by solar UV, has been implicated in skin carcinogenesis. This study aimed to investigate the mechanistic role of TOPK in solar UV-induced skin damage and tumor development. Methods: RNA sequencing (RNA-seq) was performed on skin tissues from wild-type (WT) and TOPK knockout (KO) mice, with or without solar UV exposure, to identify TOPK-regulated genes and pathways. Follow-up experiments using Western blotting, immunofluorescence, and luciferase assays were conducted in vitro and in vivo. Functional assays included 3D spheroid and Transwell co-culture systems involving cutaneous squamous cell carcinoma (cSCC) and fibroblast cells. Results: TOPK deletion altered gene expression profiles and inhibited solar UV-induced activation of multiple signaling pathways, including cytokine–cytokine receptor interaction, PI3K/AKT, MAPKs, PKG, cAMP, and calcium signaling. RNA-seq and protein analyses identified interleukin-19 (IL19) as a key downstream effector suppressed by TOPK deletion. In cSCC and fibroblast cells, TOPK knockdown reduced IL19 expression and secretion. IL19 promoted cSCC growth and activated PI3K/AKT, ERK, and TOPK pathways. Additionally, chronic TGFβ exposure increased IL19 expression and activated fibroblasts, as indicated by elevated αSMA and FAPα levels. Conclusions: These findings establish TOPK as a central regulator of solar UV-induced skin carcinogenesis, partially via modulation of IL19 signaling and fibroblast activation. Targeting TOPK may offer a novel strategy for the prevention and treatment of NMSC. Full article

Early detection and continuous monitoring of diseases are critical to improving patient outcomes, treatment adherence, and diagnostic accuracy. Traditional melanoma diagnosis relies primarily on visual assessment and biopsy, with reported accuracies ranging from 50% to 90% and significant inter-observer variability. Among emerging diagnostic technologies, Raman spectroscopy has demonstrated considerable promise for non-invasive disease detection, particularly in early-stage skin cancer identification. A portable, real-time Raman spectroscopy system could significantly enhance diagnostic precision, reduce biopsy reliance, and expedite diagnosis. However, miniaturization of Raman spectrometers for portable use faces significant challenges, including weak signal intensity, fluorescence interference, and inherent trade-offs between spectral resolution and the signal-to-noise ratio. Recent advances in silicon photonics present promising solutions by facilitating efficient light collection, enhancing optical fields via high-index-contrast waveguides, and allowing compact integration of photonic components. This work introduces a numerical analysis of an integrated digital Fourier transform spectrometer implemented on a silicon-nitride (SiN) platform, specifically designed for Raman spectroscopy. The proposed system employs a switch-based digital Fourier transform spectrometer architecture coupled with a single optical power meter for detection. Utilizing a regularized regression method, we successfully reconstructed Raman spectra in the 800 cm⁻¹ to 1800 cm⁻¹ range, covering spectra of both benign and malignant skin lesions. Our results demonstrate the capability of the proposed system to effectively differentiate various skin cancer types, highlighting its feasibility as a non-invasive diagnostic sensor. Full article

Background/Objectives: A history of cancer has been linked to stress and concerns about its recurrence. We aimed to test the benefits of an evidence-based self-help stress reduction method, the Clinical Emotional Freedom Technique (EFT), in survivors of cutaneous melanoma, and to contrast its effects on wellbeing and perceptions of cancer recurrence when delivered in a group versus individual instruction setting. Methods: This study was preregistered at clinicaltrials.gov (NCT05421988, 3 April 2022). Fifty-three patients aged 18 and above, diagnosed with melanoma (stage T1a–T2a) at least 6 months prior, and not in active treatment were recruited from a private skin cancer clinic. After consent, all participants were randomized in one step into three condition groups: Group EFT (G-EFT; n = 16), Individual EFT (I-EFT; n = 18), and a waiting-list control condition (CC; n = 19). G-EFT and I-EFT participants attended weekly treatment sessions for four weeks. Perceptions of cancer recurrence and wellbeing measures were obtained pre- and post-intervention and at three-months follow-up using online questionnaires. Subjective units of distress (SUDs) were recorded by the EFT instructor at the beginning and end of each session. Results: Two-way repeated measures ANOVAs revealed significant improvements from pre- to post-intervention in both EFT conditions in terms of participants’ understanding of how to prevent recurrence and in their spiritual wellbeing. No statistically significant effects were found for fear of recurrence, recurrence perceptions, and affect. Significant decreases in SUD scores were observed in both EFT conditions. Over 80% of the experimental conditions’ participants reported positive changes and satisfaction. Conclusions: The findings provide support for offering EFT instruction as a non-pharmacological and noninvasive self-help method to ameliorate the stress of cancer diagnosis and treatment, and for its similar effectiveness in either a group or individual format. Full article

Background: Artificial intelligence (AI) has emerged as a transformative tool in modern medicine, particularly in dermatology, where it supports the diagnosis and management of various skin diseases, including skin cancer. Through machine learning and deep learning techniques, AI enables accurate analysis of clinical and dermoscopic images, improving early detection and clinical outcomes. Objective: This systematic review aimed to evaluate the clinical applications of AI in dermatology, focusing on its impact on diagnostic accuracy, workflow efficiency, and access to specialized care. Methods: The review was conducted according to PRISMA guidelines. Peer-reviewed studies published between January 2020 and March 2025 in English or Spanish were included if they evaluated AI-based tools for dermatological diagnosis, classification, or treatment. Animal studies, editorials, non-peer-reviewed articles, and studies with an unclear methodology were excluded. A comprehensive search was performed in PubMed, Scopus, IEEE Xplore, and Google Scholar between December 2024 and March 2025. The risk of bias was assessed qualitatively, using a tailored framework based on study design, dataset transparency, and clinical applicability. Results: A total of 29 studies met the inclusion criteria. AI tools demonstrated high performance in melanoma detection, achieving up to 90% accuracy and 85% sensitivity. In clinical settings, AI support reduced mismanagement of malignant lesions from 58.8% to 4.1% and avoided 27% of unnecessary procedures in benign cases. Additional tools such as convolutional neural networks and imaging systems like FotoFinder also showed promising results. Limitations: Limitations of the evidence include the heterogeneity of AI models, lack of external validation, and a moderate-to-high risk of bias. Conclusions: AI has demonstrated robust clinical potential in dermatology, particularly in cancer detection and workflow optimization. However, further studies are required to address challenges such as algorithmic bias, data privacy, and regulatory oversight. Funding and registration: This review received no external funding and was not registered in a systematic review registry. Full article

Melanoma is a type of skin cancer that originates in the melanocytes, the epidermis’ basal layer. The skin has traditionally been an attractive administration location for drug delivery in tumor therapy, and it is composed of three layers: the outermost stratum corneum (SC), the middle epidermis, and the deepest layer, the dermis. Melanoma can be treated using a variety of methods, such as chemotherapy, surgery, radiotherapy, and biological therapy, but all are expensive and have side effects. Furthermore, the SC is the primary barrier that contributes to the impermeability of the skin, which is a limitation in epidermal drug transport and can aid in achieving effective drug concentration with minimal side effects at the target location. Microneedles (MNs) are tiny needles that are easy to use, inexpensive, and non-toxic. In recent years, MNs have been significantly studied for the treatment of melanoma due to their excellent biocompatibility, minimal invasion, high patient compliance, simple penetration process, and high SC penetration rate. Most notably, MNs can provide efficient and seldom unpleasant delivery carriers and synergistic effectiveness by combining multi-model techniques with immunotherapy, gene therapy, photodynamic therapy (PDT), and photothermal treatment (PTT). This review will focus on biocompatibility, biodegradability, limitations, fabrication materials, release mechanisms, and delivery of the therapeutics of MNs for melanoma treatment. Full article

The skin microbiome is identified as one of the crucial factors in several pathological conditions, including its potential capacity in modulating cancer progression and response to treatment. A strong association of Bacilli and Betaproteobacteria classes and the Bacteroidetes phylum with melanoma is described in patients with cutaneous malignancies, while an imbalance of S. epidermidis and S. aureus is related to the progression of other skin cancers. In the present study, we characterized the microbial community in suspected lesions of 35 patients, classified, after histological analysis, as malignant melanoma lesions and benign non-melanoma lesions. Mirrored healthy skin were also included as negative control. No significant difference in alpha and beta diversity was observed when samples were categorized in four different groups (melanoma samples vs. contralateral healthy samples; melanoma samples vs. benign lesions; benign lesions vs. contralateral controls; melanoma controls vs. benign controls). The differential abundance analyses show that Corynebacterium urealyticum is more abundant in melanoma samples compared to their control, while Roseomonas gilardii is less abundant in melanoma. Staphylococcus massiliensis, Bacillus coagulans, Paracoccus yeei, Corynebacterium jeikeium, and Corynebacterium pyruviciproducens are present only in melanoma samples when compared with benign lesions. Full article

Background/Objectives: Systemic sclerosis (SSc) is associated with high malignancy risk. With improving SSc management, tumor risk could change, therefore re-evaluating the possibility of neoplasms is necessary. Our aim was to observe malignancy prevalence and its risk factors in the Hungarian SSc population, comparing them to our previous and international results. Methods: We retrospectively collected the data of SSc patients followed by and admitted to three Hungarian clinical centers between 2018 and 2024. The collected data included the characteristics of SSc and neoplasms, autoantibody positivities, immunosuppressive treatments, pregnancy and environmental factors. Results: Out of 541 patients, 85 had malignancy and, in total, 96 tumors were registered. Skin cancer was the most common (n = 24), followed by breast (n = 14) and lung cancer (n = 14). Among skin cancers, almost one-third was melanoma. Tumors mostly appeared in two peaks: around the time of SSc diagnosis and 10 years later. The occurrence of anti-RNA Polymerase III (anti-RNAPIII) was significantly higher in cancerous patients. Tumor risk was higher with anti-RNAPIII (Odds Ratio (OR) 4.33, 95% Confidence Interval (95% CI) 1.08, 15.1) and anti-topoisomerase I (ATA) (OR 2.34, 95% CI 0.94, 5.84) positivity. Women and patients with diffuse cutaneous SSc (dcSSc) were more likely to have malignancy. Smoking (OR 1.27, 95% CI 0.53, 3.00) also raised the possibility of carcinogenesis. Cancerous patients were older (p-value = 0.003), and their mortality was worse compared to non-cancerous patients (Hazard Ratio (HR) 4.75, 95% CI 2.12, 10.62). Pregnancy did not provide a protective effect against breast cancer. Conclusions: Malignancy significantly contributes to the increased mortality in SSc. Female gender, dcSSc, anti-RNAPIII positivity, smoking and older age represent a higher risk of tumors. Dermatological cancer screening is necessary for all patients with SSc. Full article

Skin cancer, particularly melanoma, is one of the leading causes of cancer-related deaths. It is essential to detect and start the treatment in the early stages for it to be effective and to improve survival rates. This study developed and evaluated a deep learning-based classification model to classify the skin lesion images as benign (non-cancerous) and malignant (cancerous). In this study, we used the ISIC 2016 dataset to train the segmentation model and the Kaggle dataset of 10,000 images to train the classification model. We applied different data pre-processing techniques to enhance the robustness of our model. We used the segmentation model to generate a binary segmentation mask and used it with the corresponding pre-processed image by overlaying its edges to highlight the lesion region, before feeding it to the classification model. We used transfer learning, using ResNet-50 as a backbone model for a feedforward network. We achieved an accuracy of 92.80%, a precision of 98.64%, and a recall of 86.80%. From our study, we have found that integrating deep learning techniques with proper data pre-processing improves the model’s performance. Future work will focus on expanding the datasets and testing more architectures to improve the performance metrics of the model. Full article

Background/Objectives: The increasing incidence of cancer during pregnancy is a growing public health concern, driven by delayed parenthood and rising maternal age. Pregnancy-associated cancer (PAC) presents complex clinical challenges, necessitating a balance between maternal cancer treatment and fetal safety. Historically considered incompatible with favorable pregnancy outcomes, evidence now suggests that pregnancy can often proceed without affecting cancer prognosis. A 2022 study in Italy provided the first population-based PAC estimates by linking cancer registries (CRs) and hospital discharge records (HDRs). This study aimed to update PAC estimates to 2019, covering 30% of the Italian population and addressing prior data limitations. Methods: A retrospective longitudinal analysis was conducted on women aged 15–49 diagnosed with malignant cancers between 2003 and 2019. Data from 21 Italian CRs were linked with HDRs to identify PAC cases, defined as obstetric hospitalizations occurring for women diagnosed with cancer in our study cohort in the period spanning from one year before to two years after a cancer diagnosis. All malignant cancers, excluding non-melanoma skin cancers, were analyzed. PAC rates were calculated per 1000 pregnancies, and trends were assessed using log-linear and JoinPoint regression models. Results: Among 131,774 women diagnosed with cancer, 6329 PAC cases were identified, with a PAC rate of 1.43 per 1000 pregnancies, consistent with global estimates. Thyroid (24.4%) and breast cancer (23.2%) were the most common. Analyzing the PAC rate by pregnancy outcome, in the period 2015–2019, this increased for both childbirths and miscarriages but decreased for voluntary terminations. Most hospitalizations (54%) occurred pre-diagnosis, peaking at diagnosis, especially for breast cancer (69%). Conclusions: PAC incidence is rising, particularly for live births and miscarriages, underscoring the need for multidisciplinary care and robust epidemiological insights to guide clinical management. Full article

Cutaneous metastatic melanoma (CMM) is the most aggressive form of skin cancer, with characteristics including a poor prognosis, chemotherapy-induced secondary tumorigenesis, and the emergence of drug resistance. Our recent study demonstrated that triphenyl phosphonium (TPP)-based nanovesicles (BPPB), which have amphiphilic properties, exert potent ROS-dependent anticancer effect against PLX4032 (PLX)-sensitive MeOV BRAF^V600E and MeTRAV BRAF^V600D mutant cell lines, evidencing more marked efficacy on MeOV cells. Here, taking advantage of this in vitro model, the antitumoral effect of BPPB was tested on PLX-resistant (PLX-R) MeOV BRAF^V600E and MeTRAV BRAF^V600D mutant cell lines to find a new potential strategy to fight melanoma therapy resistance. Specifically, we investigated both its effects on cell viability in dose- and time-dependent experiments and those on ROS generation. Our results show that BPPB exerted strong antiproliferative effects, regardless of their acquired resistance of cells to PLX, that correlated with ROS overproduction for 24 h treatments only. Moreover, in terms of cell viability, PLX-R MeTRAV cells demonstrated a remarkably higher tolerance to 24 h BPPB treatment than PLX-R MeOV. On the contrary, BPPB exposure for longer periods induced similar responses in both cell lines (IC₅₀ = 87.8–106.5 nM on MeOV and 81.0–140.6 nM on MeTRAV). Notably, BPPB cytotoxicity on non-tumorigenic human keratinocytes (HaCaT) was low, thus establishing that BPPB is appreciably selective for CMM cells, allowing for selectivity index values (SIs) up to 11.58. Furthermore, the BPPB concentration causing 50% hemolysis (HC₅₀) was found to be 16–173 and 4–192-fold higher than the IC₅₀ calculated for PLX-R MeOV and MeTRAV cells, respectively. Correlation studies established that BPPB exerts cytotoxic effects on PLX-R MeOV and MeTRAV cells by a time-dependent mechanism, while a concentration-dependent mechanism was observed only at 24 h of exposure. Finally, a ROS-dependent mechanism can be assumed only in PLX-R MeTRAV cells in 72 h treatment. Full article